The most recent information on Ras85D is here. Click here for the function of Ras85D. Edit this page in Wiki Genes - Ras85D or see Wiki Gene. Dual function of Ras in Raf activation. Paper-1718960. Ras1 is also epistatic to K10. Paper-927043. KSR: a MAPK scaffold of the Ras pathway? Paper-8830643. It acts upstream of Raf and downstream of Ras. Paper-1019064. Ras and Rap: are former enemies now friends? Paper-10770021. The love-hate relationship between Ras and Notch. Paper-10804930. Epistatic analysis placed clown between argos and Ras1. Paper-8359828. Dynamic EGFR- Ras signalling in Drosophila leg development. Paper-11154912. Thus, Nf1 signals through Ras/ MAPK in Drosophila. Paper-9068046. Activation of ERK/ MAPK is a key event downstream of RAS. Paper-1903141. Two of these genes (termed Dras 1 and Dras 2) were sequenced. Paper-4788133. RIC, a calmodulin- binding Ras-like GTPase. Paper-797946. CNK, a RAF- binding multidomain protein required for RAS signaling. Paper-1638354. The Egfr/ Ras pathway mediates this function of the peripodial membrane. Paper-9964343. Rap1 belongs to the highly conserved Ras subfamily of small GTPases. Paper-9993293. Drosophila Jun mediates Ras-dependent photoreceptor determination. Paper-133670. These effects result from enhanced activity of the EGFR/ Ras signalling pathway. Paper-8513355. Initial studies in mammalian cells suggested a role for Rap as a Ras antagonist. Paper-1754335. Input from Ras is required for maximal PI(3)K signalling in Drosophila. Paper-12299894. Ectopic expression of PTP-ER dramatically inhibits RAS1/ MAPK signaling. Paper-1903141. RAF is a critical effector of the small GTPase RAS in normal and malignant cells. Paper-11372851. The Ral GTPase is activated by RalGDS, which is one of the effector proteins for Ras. Paper-1948391. 14-3-3 epsilon positively regulates Ras-mediated signaling in Drosophila. Paper-1019063. We found that Ras- mediated Dp110 regulation is dispensable for viability. Paper-12299894. It has been proposed that RasGAP may also function as an effector of Ras activity. Paper-8456210. Regulation of cone cell formation by Canoe and Ras in the developing Drosophila eye. Paper-1108438. The small GTPase Rap1 was originally thought to function as an antagonist of Ras. Paper-10770021. A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/ MAPK. Paper-9068046. Signalling by the sevenless protein tyrosine kinase is mimicked by Ras1 activation. Paper-52863. Egfr/ Ras signaling promotes vein cell fate specification in the developing Drosophila wing. Paper-12529256. The Egfr, ras and raf genes are each found to be essential for recruitment of R1-R7 cells. Paper-8821052. Raf functions downstream of Ras1 in the Sevenless signal transduction pathway. Paper-77737. Our data do not support the paradigmatic model where Ral is in the effector pathway of Ras. Paper-9685202. As with Egfr, loss of ras or raf perturbs the spacing and arrangement of R8 precursor cells. Paper-8821052. Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Paper-9543689. Thus the Ras/ Raf pathway also appears to be essential for G-protein-coupled neurotransmission. Paper-266863. At least two suppressors appear to function either between Ras1 and Raf or in parallel to Raf. Paper-658805. Drosophila TFIIA-S is up-regulated and required during Ras-mediated photoreceptor determination. Paper-470547. Therefore, spen encodes a positively acting component of the DER/ Ras signaling pathway. Paper-8543275. The Dmras64B and Dmras85D transcripts were analyzed by blot hybridization and shown to be dissimilar. Paper-5729204. The jing and ras1 pathways are functionally related during CNS midline and tracheal development. Paper-10650408. PTP-ER mutants produce extra R7 cells and enhance activated Ras1 signaling. Paper-1903141. Each response requires the same Ras, Raf, MAPK, and Pnt signal transduction pathway. Paper-9855273. Negative regulation of Egfr/ Ras pathway by Ultrabithorax during haltere development in Drosophila. Paper-12176473. NF1 appears to regulate the rutabaga- encoded adenylyl cyclase rather than the Ras- Raf pathway. Paper-987550. Of these sites, the CRE seems to function primarily in the response to Ras, the secondary signal of Dpp. Paper-1490830. Recent advances in these systems reveal some of the mechanisms by which Ras and Notch can interact. Paper-10804930. The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway. Paper-209497. These results suggest that Lozenge is involved in the Yan/Pointed dynamic in a Ras-dependent manner. Paper-9597422. Our study provides in vivo evidence that Raf can be activated by an RTK in a Ras-independent pathway. Paper-209497. These rescuing effects of p21v- ras are dependent on the presence of maternally derived D-raf activity. Paper-86563. Control of cell fate determination by p21ras/ Ras1, an essential component of torso signaling in Drosophila. Paper-86563. We show that the three different functions of Ras are mediated by distinct thresholds of MAPK activity. Paper-8774503. Role of the EGFR/ Ras/ Raf pathway in specification of photoreceptor cells in the Drosophila retina. Paper-8821052. Genetic interactions, however, suggested a Ras-independent role for RasGAP in the regulation of growth. Paper-1767493. Interestingly, DRacGAP expression is negatively regulated by the EGFR/ Ras pathway in these regions. Paper-8513355. Egfr/ Ras pathway mediates interactions between peripodial and disc proper cells in Drosophila wing discs. Paper-9964343. DRacGAP, a novel Drosophila gene, inhibits EGFR/ Ras signalling in the developing imaginal wing disc. Paper-8513355. We find that signaling through the EGFR/ RAS/ MAPK pathway is necessary and limiting for AMP proliferation. Paper-13574104. Ras1, the Drosophila homologue of p21, and the Rlb1 protein, are also non-cytoplasmic, membranous proteins. Paper-174755. Coactivation of STAT and Ras is required for germ cell proliferation and invasive migration in Drosophila. Paper-10159054. In addition, Ras1 is essential for the activation of an additional factor which in turn activates Draf. Paper-1718960. JNK- and Fos- regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. Paper-12317756. Ras is known to mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye. Paper-14560891. The Drosophila secreted protein Argos regulates signal transduction in the Ras/ MAPK pathway. Paper-945332. Embryos mutant for stat92E or Ras1 have fewer PGCs, and these cells migrate slowly, errantly, and fail to coalesce. Paper-10159054. This response for pb implicates at least two signal transduction pathways, those involving Ras1 and Notch. Paper-1559810. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. Paper-86642. GAL4- EcR is activated in the FC by an ecdysone agonist and repressed by tissue-specific Ras GTPase signals. Paper-13210528. Ras signaling modulates activity of the ecdysone receptor EcR during cell migration in the Drosophila ovary. Paper-13210528. Geminin and Brahma act antagonistically to regulate EGFR- Ras- MAPK signaling in Drosophila. Paper-15194275. Spitz/ EGFr signalling via the Ras/ MAPK pathway mediates the induction of bract cells in Drosophila legs. Paper-9424160. The genomic sequences of Dmras85D and Dmras64B were determined and shown to differ from previously published sequences. Paper-5729204. Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway. Paper-1822356. Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophila eye. Paper-14560891. A gene termed Rlb1 is located nearby and upstream of Ras1, and is oriented in the opposite polarity relative to Ras1. Paper-174755. Reciprocal regulatory interactions between the Notch and Ras signaling pathways in the Drosophila embryonic mesoderm. Paper-9428961. Our analysis indicates that corkscrew function is still required during signaling by activated forms Ras1 and Raf proteins. Paper-536019. The expression of Rlc1 during embryogenesis is similar, but not identical, to the expression pattern detected for Ras1. Paper-174755. Deregulation of the Egfr/ Ras signaling pathway induces age-related brain degeneration in the Drosophila mutant vap. Paper-9748713. Ras1-dependent signaling by ectopically- expressed Drosophila src gene product in the embryo and developing eye. Paper-7669871. The Drosophila 14-3-3 protein Leonardo enhances Torso signaling through D-Raf in a Ras 1-dependent manner. Paper-1238895. We observe dominant interactions between Ras1 mutants and other dorsoventral pathway mutants, including Egfr(top) and gurken. Paper-927043. The data suggest that the divergence of the Dmras genes was ancient, and that Dmras85D and Dmras64B have different functions. Paper-5729204. The SH2-containing tyrosine phosphatase corkscrew is required during signaling by sevenless, Ras1 and Raf. Paper-536019. Ras-independent activation of ERK signaling via the torso receptor tyrosine kinase is mediated by Rap1. Paper-10804786. Here, we identify the Drosophila Ral homologue RalA as a new key regulator of polar-cell differentiation during oogenesis. Paper-12862366. Thus, the DNA-binding protein Cic is a key downstream component in the pathway by which Ras regulates growth in imaginal discs. Paper-13185984. We recently isolated a gene called split ends ( spen) in a screen designed to identify new components of the RTK/ Ras pathway [5]. Paper-8543275. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. Paper-259792. Antagonistic regulation of Yan nuclear export by Mae and Crm1 may increase the stringency of the Ras response. Paper-10773132. Activated RIC, a small GTPase, genetically interacts with the Ras pathway and calmodulin during Drosophila development. Paper-10774788. We have used Drosophila embryos to examine the mechanism of Raf ( Draf) activation in the complete absence of p21(Ras) ( Ras1). Paper-1718960. In a screen for calmodulin-binding proteins, we identified RIC, a protein related to the Ras subfamily of small GTPases. Paper-797946. We now show that two other Rho subfamily proteins, Dcdc42 and RhoA, as well as Ras1 are also required for dorsal closure. Paper-1781059. The activity of Mblk-1, a mushroom body-selective transcription factor from the honeybee, is modulated by the ras/ MAPK pathway. Paper-9708302. The Ras-related Rap GTPases are highly conserved across diverse species but their normal biological function is not well understood. Paper-1754335. These results provide evidence that Argos negatively regulates signal transduction events in the Ras/ MAPK cascade. Paper-945332. Thus, Argos- induced cell death seemed to have resulted from the suppression of the anti-apoptotic function of Ras. Paper-1822356. We find that in the wing disc, DRac1 enhances EGFR/ Ras-dependent activation of MAP Kinase in the prospective veins. Paper-8513355. In Drosophila, as in many other animals, EGFR- Ras signalling has multiple developmental roles from oogenesis to differentiation. Paper-11154912. Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/ ras signaling pathway. Paper-13185984. The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/ MAPK pathway. Paper-126667. Our study provides the first evidence that Src42A defines a negative regulatory pathway parallel to Ras1 in the RTK signaling cascade. Paper-1816552. Drosophila yan is one of a few downstream components identified to date, functioning as an antagonist of the RTK/ Ras/ MAPK pathway. Paper-2125472. To address the physiological role of this Ras subfamily in vivo, activated forms of the Drosophila Ric gene were introduced into flies. Paper-10774788. Sequence analysis of three dominant-negative alleles defines two regions of 14-3-3 epsilon that participate in RAS1 signaling. Paper-1019063. Yan, an ETS family transcriptional repressor, is regulated by receptor tyrosine kinase signaling via the Ras/MAPK pathway. Paper-10485621. Drosophila yan has been postulated to act as an antagonist of the proneural signal mediated by the sevenless/ Ras1/ MAPK pathway. Paper-259770. To demonstrate that p21ras/ Ras1 mediates tor signaling, we injected mammalian p21ras variants into early Drosophila embryos. Paper-86563. These were GOF phenotypes mediated by increased RAS/ MAPK signaling and requiring the LS mutant's residual phosphatase activity. Paper-13495147. Hh controls dorsal mesodermal Ras signaling by transcriptional regulation of the EGF receptor ligand protease, encoded by rhomboid (rho). Paper-11376357. We therefore suggest that Ras plays a critical role in the dynamic regulation of border cell migration via a Raf-independent pathway. Paper-539291. We found that expression of an activated form of Ras1 during oogenesis resulted in embryos with tor gain-of-function phenotypes. Paper-86563. We also show that endogenous Ras is required to maintain normal levels of dMyc, but not dPI3K signaling during wing development. Paper-9543689. Genetic interactions with Rap1 and Ras1 reveal a second function for the fat facets deubiquitinating enzyme in Drosophila eye development. Paper-1238720. DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila. Paper-589407. Similar types of interactions in mammals may be important for determining whether and how alterations in Ras or Notch lead to cancer. Paper-10804930. CONCLUSION: In the Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and Hid activities. Paper-14560891. Alphabet, a Ser/Thr phosphatase of the protein phosphatase 2C family, negatively regulates RAS/ MAPK signaling in Drosophila. Paper-12004544. Activation of the EGFR/ Ras pathway appears to promote proneural gene self-stimulation mediated by the SMC-specific enhancers. Paper-8682613. Using a simple loss-of-function 14-3-3 epsilon mutation, we show that 14-3-3 epsilon acts to increase the efficiency of RAS1 signaling. Paper-1019063. Low levels of Ras activity at the posterior pole direct tll but not hkb transcription; higher levels drive transcription of both genes. Paper-1287379. During vein formation, local DRacGAP repression would ensure maximal activity of Rac and, in turn, of Ras pathways in vein territories. Paper-8513355. The effects of C3G overactivity can be suppressed by reducing the gene dose of components of the RAS- MAPK pathway and of RAP1. Paper-1722782. Transient misexpression of the activated Ras1 protein (Ras1V12) later in pupal development suppressed the Argos-induced cell death. Paper-1822356. Ras upregulated the growth driver dMyc, and both Ras and dMyc increased levels of cyclin E posttranscriptionally. Paper-2128408. These findings suggest that, prior to Ras activation, the Mae/ Yan interaction blocks premature nuclear export of Yan monomers. Paper-10773132. These results argue that photoreceptor differentiation is regulated by the RAS pathway through targeted proteolysis of the TTK repressor. Paper-1125717. PTP-ER, a novel tyrosine phosphatase, functions downstream of Ras1 to downregulate MAP kinase during Drosophila eye development. Paper-1903141. The Ras and Notch signaling pathways are used over and over again during development to control many different biological processes. Paper-10804930. Egfr/ Ras signaling regulates DE-cadherin/ Shotgun localization to control vein morphogenesis in the Drosophila wing. Paper-12529256. Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras. Paper-11329244. Both the lethality and the eye roughening caused by activated Dsrc were partially suppressed by mutations in the Drosophila Ras1 gene. Paper-7669871. We suggest that Ras- PI3K- Akt activity in the peripheral glia promotes growth of the perineurial glia by inhibiting FOXO. Paper-12402224. We also present genetic evidence suggesting that Raf acts downstream of Ras1 and upstream of Sina in this signal transduction cascade. Paper-77737. In eye and wing development Jun participates in a separate signaling pathway that is comprised of Ras, Raf, and the ERK-type kinase Rolled. Paper-1099543. Down-regulation requires the presence of Phyllopod ( PHYL), which is induced by the RAS pathway, and Seven In Absentia ( SINA). Paper-1125717. Novel gain-of-function mutations in the Drosophila Rap1 and Ras1 genes are described herein that interact genetically with fat facets mutations. Paper-1238720. Here, we demonstrate that the Ras- MAPK pathway is involved in synaptic plasticity at the Drosophila larval neuromuscular junction. Paper-9418112. Our results suggest that KSR is a general and evolutionarily conserved component of the RAS signaling pathway that acts between RAS and RAF. Paper-438577. Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/ MAPK pathway. Paper-259770. In the somatic mesoderm, Hbs is restricted to fusion competent myoblasts and is regulated by Notch and Ras signaling pathways. Paper-9085471. MKP-3 has essential roles as a negative regulator of the Ras/ mitogen-activated protein kinase pathway during Drosophila development. Paper-10215641. Conversely, Hh overexpression can fully inhibit Lbe even when Ras signaling is much reduced, suggesting that Hh also acts in parallel to Ras. Paper-11376357. We observed that mechanosensory bristles induced bract fate in neighbouring epidermal cells, and that the RAS/ MAPK pathway mediated this induction. Paper-9424160. Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling. Paper-8456210. Our findings reveal that Ras and Notch do not function independently; rather, we have uncovered several modes of cross-talk between these pathways. Paper-9428961. We found that the injection of activated p21v- ras rescued the maternal- effect phenotypes of both tor and csw null mutations. Paper-86563. By using a recently developed technique of germline mosaics, we find that D-Raf can be activated by torso in the complete absence of Ras1. Paper-209497. Mediation of PACAP-like neuropeptide transmission by coactivation of Ras/ Raf and cAMP signal transduction pathways in Drosophila. Paper-266863. One insertion was in the gene encoding Ras GTPase-activating protein; its overexpression phenotype was strongly enhanced by a mutation in Ras1. Paper-775282. These interactions suggest that Rin is required as an effector in Ras signaling during eye development, supporting an effector role for RasGAP. Paper-8456210. Genetic data suggests that phyl acts downstream of Ras1, raf, and yan to promote neuronal differentiation in this subset of photoreceptors. Paper-165984. These results demonstrate a requirement of Jun downstream of the sevenless/ ras signaling pathway for neuronal development in the Drosophila eye. Paper-133670. Conversely, overexpression of Hh or increasing Ras signaling eliminates Lbe expression while expanding Eve within the cardiogenic mesoderm. Paper-11376357. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Paper-46238. These data suggest that Rin is not a general component of polarity generation, but serves a function specific to Ras and RhoA signaling pathways. Paper-8456210. The 14-3-3 epsilon protein appears to function in multiple RTK pathways, suggesting that it is a general component of RAS1 signaling cascade. Paper-1019063. Unlike Egfr(top) and gurken mutants, however, Ras1 females are moderately fertile, laying eggs with ventralized eggshells that can hatch normal larvae. Paper-927043. We found that the pro-survival function of five genes ( Ras85D, Cp1, CG13784, CG32016, and CG33087), was dependent on ecdysone signaling. Paper-13615250. During differentiation, the Ras signaling cascade alters the Yan/Pointed dynamic through protein phosphorylation, effecting a developmental switch. Paper-9597422. Our genetic data suggest that 14-3-3 epsilon functions downstream of or parallel to RAF, but upstream of nuclear factors in RAS1 signaling. Paper-1019063. Both the expression pattern and the subcellular localization are consistent with the proposed function of 14-3-3 proteins in Ras/ Raf/MAPK signaling. Paper-1019064. Characterization of Src42A mutations shows that Src42A acts independent of Ras1 and that it is, unexpectedly, a negative regulator of RTK signaling. Paper-1816552. Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes. Paper-10609009. Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS- MAPK pathway and RAP1. Paper-1722782. Ras1+ is a positive modifier of pb activity both in normal and ectopic cell contexts, while the Ras1-antagonist Gap1 has an opposite effect. Paper-1094031. Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase signaling in oogenesis: cytoplasmic retention and degradation. Paper-1419817. Furthermore, we have used the dominantly inhibiting corkscrew allele to examine the role of corkscrew during signaling by activated forms of Ras1 and Raf. Paper-536019. Overexpression of Argos, a diffusible inhibitor of the EGF receptor and Ras signaling, caused excessive cell death in developing eyes at pupal stages. Paper-1822356. Dof is an intracellular protein that is essential for signal transmission by the FGFR and acts downstream of the receptor and upstream of Ras. Paper-1631705. Genetic interaction and epistasis experiments indicate that heartbroken acts downstream of the two FGF receptors but either upstream of or parallel to RAS1. Paper-1683471. Connector enhancer of KSR ( CNK) is a multidomain-containing protein previously identified as a positive regulator of the RAS/ MAPK pathway in Drosophila. Paper-10008760. Our data suggest that the modulation occurs by a mechanism independent of transcriptional control of the homeotic loci themselves, or of the Ras1/ Gap1 genes. Paper-1094031. Analysis of these genetic interactions reveals that Fat facets has an additional function later in eye development involving Rap1 and Ras1 proteins. Paper-1238720. Restriction of high-level prospero expression to the R7 cell appears as a subsequent event, which requires Sevenless activation of the Ras1/MAP kinase pathway. Paper-698906. Despite their ability to bind activated Rap as well as activated Ras, they seem to act downstream of Ras but not downstream of Rap. Paper-9685202. A KSR/ CNK complex mediated by HYP, a novel SAM domain-containing protein, regulates RAS-dependent RAF activation in Drosophila. Paper-11372851. Moreover, our data suggest that the interaction of KSR to CNK/ HYP stimulates the RAS-dependent RAF- activating property of KSR. Paper-11372851. Consistent with this, the eye phenotype of flies expressing a sev- Ras1 construct is modulated by PDS and dTAF(II)16 in a gene dosage-dependent manner. Paper-8689566. These results show that RasGAP can function as an inhibitor of signaling pathways mediated by Ras and receptor tyrosine kinases in vivo. Paper-1767493. Gene dosage studies among ventrolateral genes suggest that the rho product (Rho) may facilitate Spi- EGF-R signaling, resulting in activation of RAS. Paper-91735. The peptide induced a 100-fold enhancement of potassium currents by activating the Ras- Raf and adenylyl cyclase-adenosine 3',5'-monophosphate ( cAMP) pathways. Paper-987550. We demonstrate that the role of Ras1 in Draf activation is not limited to the translocation of Draf to the membrane through a Ras1- Draf association. Paper-1718960. This suggests that PP2A both negatively and positively regulates the Ras1 cascade by dephosphorylating factors that function at different steps in the cascade. Paper-510248. Components of the signal transduction pathway activated by Sev in the R7 precursor include proteins encoded by the gap1, drk, Sos, ras1 and raf loci. Paper-117924. Loss-of-function mutations in components of the Ras/ MAPK signaling cascade act as dominant suppressors of the phenotype caused by the argos null mutations. Paper-945332. Our results show that, in addition to constitutive transcripts, the src, abl, ras1 and ras3 genes express a set of maternal/embryonic-specific transcripts. Paper-6145302. Finally, activation of the Egfr signaling pathway by either ectopically secreted Spitz, or activated Ras, leads to the ectopic expression of Delilah. Paper-1202857. Previous analyses have demonstrated that Ras1 (p21ras) operates upstream of the D-Raf ( Raf1) serine/ threonine kinase in this signaling pathway. Paper-209497. EGFR is not essential for R8 cell specification, either alone or redundantly with any other receptor that acts through Ras or Raf, or by activating MAP kinase. Paper-8821052. Two of these correspond to mutations in ras-1 and Son of sevenless (Sos), which also function in the sevenless and EGF receptor ( Der) tyrosine kinase pathways. Paper-86546. Localised activation of the Ras/Raf pathway by Epidermal Growth Factor Receptor ( EGFR) signalling specifies the formation of veins in the Drosophila wing. Paper-9385330. The cellular signal transduction pathways by which C3G, a RAS family guanine nucleotide exchange factor, mediates v-crk transformation are not well understood. Paper-1722782. Like its mammalian homolog, Drosophila RasGAP stimulated the intrinsic GTPase activity of normal mammalian H- Ras but not that of the oncogenic Val12 mutant. Paper-1767493. Using MGC-targeted expression, we found that increased Ras signaling rescued the lethality associated with expression of a dominant-negative spen transgene. Paper-8543275. The effect of leo requires D-Raf and Ras1 activities but not KSR or DOS, two recently identified essential components of Drosophila RTK signaling pathways. Paper-1238895. Here, we show that the HMG-box protein Capicua ( Cic) restricts cell growth in Drosophila imaginal discs, and its levels are, in turn, downregulated by Ras signaling. Paper-13185984. In the syncytial blastoderm embryo, activation of Tor triggers the Ras/ Raf/MEK pathway that controls the transcription of tailless ( tll). Paper-1238895. We show that Ras1- mediated signaling pathways in Drosophila are not influenced by Rap1 levels, suggesting that Ras1 and Rap1 function via distinct pathways. Paper-1754335. Thus, we propose that MAE plays multiple independent roles in fine-tuning the levels of POINTED and YAN activity in accordance with changing RTK signaling conditions. Paper-9657454. Furthermore, combined deficiencies of D-Ras1 and D-Rap1 completely abolished expression of these genes, mimicking the phenotype observed in embryos lacking D-Raf. Paper-10804786. Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Ras1, Sos, Gap1 and sina (refs 4-8). Paper-77737. A general role for Ras1 in homeotic function is likely, since Ras1+ activity also modulates functions of the homeotic loci Sex combs reduced and Ultrabithorax. Paper-1094031. Thus, Dp110 integrates inputs from its phosphotyrosine- binding adaptor and Ras to achieve maximal PI(3)K signalling in specific biological situations. Paper-12299894. Two identified interacting genes were the proto-oncogene Ras1 and its functional antagonist Gap1, prominent intermediaries in known signal transduction pathways. Paper-1094031. Both Ras1 and MAPK are expressed at the neuromuscular junction, and modification of their activity levels results in an altered number of synaptic boutons. Paper-9418112. We show here that rasp is also essential for the developmental functions of Spitz, a ligand for the Drosophila epidermal growth factor receptor ( EGFR). Paper-10821160. Genetic evidence indicates that Ras antiapoptotic activity in the developing eye is regulated by the Drosophila EGF receptor and operates through the Raf/ MAPK pathway. Paper-1638352. However, the physiological roles of MKP-3 and the mechanism by which MKP-3 regulates Ras/Drosophila ERK ( DERK) signaling in vivo have not been determined. Paper-10215641. The immunoglobulin-like protein Hibris functions as a dose-dependent regulator of myoblast fusion and is differentially controlled by Ras and Notch signaling. Paper-9085471. Conversely, overexpression of RSK dramatically suppressed the ERK-dependent differentiation, which was further augmented by mutations in the Ras/ ERK pathway. Paper-12062836. The Ras1- mitogen-activated protein kinase signal transduction pathway regulates synaptic plasticity through fasciclin II-mediated cell adhesion. Paper-9418112. This includes differential responses to EGF receptor vs. fibroblast growth factor receptor signaling as well as to more downstream components such as Ras1 and pointed. Paper-13707735. We also report our intriguing observation that complete inactivation of E1 causes non-autonomous activation of Ras-ERK in adjacent tissue, mimicking oncogenic Ras overexpression. Paper-13730953. We describe developmental roles of a novel negative regulator of Ras signaling, EDL/ MAE, a protein with an Ets-specific Pointed domain but not an ETS DNA-binding domain. Paper-9971781. We propose that the Eve precursors next to the Hh stripe are distinguished from more distant Lbe precursors by locally augmenting Ras signaling via elevating rho transcripts. Paper-11376357. Here, we show that the expression of the small subunit of TFIIA ( dTFIIA-S) is specifically up-regulated in a transient manner during Ras-mediated photoreceptor induction. Paper-470547. We show that the N-terminal Drk SH3 domain is primarily responsible for binding to the tail of Sos in vitro, and for signalling to Ras in vivo. Paper-259792. We show that the activities of two Ets-related transcription factors required for normal eye development in Drosophila, pointed and yan, are regulated by the Ras1/ MAPK pathway. Paper-126667. These results suggest that the products of these three genes may participate in a signaling pathway involving both Ras and Sina, possibly by functionally linking these two proteins. Paper-140518. Autophosphorylated Sevenless initiates a Ras1-mediated cascade, which eventually activates transcription factors in the nucleus via Raf1 and MAP kinases, resulting in R7 development. Paper-125565. Midline glia development occurs in two steps, both of which depend on the activation of the Drosophila EGF-receptor homolog and subsequent ras1/ raf-mediated signal transduction. Paper-1152287. Midline glia development occurs in two steps, both of which depend on the activation of the Drosophila EGF-receptor homolog and subsequent ras1/ raf-mediated signal transduction. Paper-1030904. These results provide evidence for a Ras-dependent signaling cascade that regulates fasciclin II-mediated cell adhesion at synaptic terminals during synapse growth. Paper-9418112. The mammalian Rit and Rin proteins, along with the Drosophila homologue RIC, comprise a distinct and evolutionarily conserved subfamily of Ras-related small GTP-binding proteins. Paper-10774788. We find that dominant negative (N17) versions of Rac and Cdc42 cause a very similar defect in migration as loss of integrins, while those of Rho and Ras have no effect. Paper-8342123. We show that both lozenge isoforms are expressed during eye development and that the relative ratio of the transcripts for the two isoforms is sensitive to changes in Ras activity. Paper-11084200. Together, our studies suggest that DRaf's extended N terminus may assist in its association with the upstream activators ( Ras1 and Rap1) through a CRN-mediated mechanism(s) in vivo. Paper-14679094. These patterns, together with genetic data obtained by different mutant conditions for EGFR- Ras members and transgene expression, suggest two rounds of signalling in leg development. Paper-11154912. Mutations in rin/G3BP genetically interact with components of the Ras signaling pathway that function at the level of Ras and above, but not with Raf/ MAPK pathway components. Paper-8456210. The protein tyrosine phosphatase Corkscrew ( CSW) is a common component of many RTK signaling pathways, and is required for signaling downstream of SEV and EGFR. Paper-9353128. A Ral guanine exchange factor- Ral pathway is conserved in Drosophila melanogaster and sheds new light on the connectivity of the Ral, Ras, and Rap pathways. Paper-9685202. We now show that two regulators of EGF signaling, argos and sprouty ( sty), and a gain-of-function Ras85D allele, interact genetically with fz in ommatidial polarity. Paper-9970332. Overexpressing the repressor form of Cubitus interruptus ( Ci), a Hh pathway antagonist, also results in expansion of Lbe at the expense of Eve, as does lowering Ras signaling. Paper-11376357. These results suggest that Mblk-1 is a transcription factor that might function in the mushroom body neuronal circuits downstream of the Ras/ MAPK pathway in the honeybee brain. Paper-9708302. These proteins, KSR, CNK, and Sur-8, can interact with multiple core components of the Ras/ MAP kinase cascade and may contribute to the structural organization of this cascade. Paper-9156038. Based on our results, we propose that MASK is a novel mediator of RTK signaling, and may act either downstream of MAPK or transduce signaling through a parallel branch of the RTK pathway. Paper-9353128. In yeast two-hybrid assays, stronger interactions between DRaf's Ras binding domain (RBD) and the small GTPase Ras1, as well as Rap1, were observed when CRN and RBD sequences were linked. Paper-14679094. Together, these findings suggest that the integration of RTK- induced RAS and Src42 signals by CNK as a two-component input is essential for RAF activation in Drosophila. Paper-10782006. When a constitutively active form of Ras1 (Ras1V12) is expressed in the R7 equivalence group cells using the sev promoter (sev-Ras1V12), additional cone cells are formed in the ommatidium. Paper-1108438. We also provide genetic and biochemical evidence that klumpfuss regulates this process through down-regulation of the Epidermal Growth Factor Receptor/ dRas1 signaling pathway. Paper-10457232. The integration of Pointed with the combinatorial effects of dTCF, Mad, Twist, and Tinman determines inductive Ras signaling specificity in muscle and heart development. Paper-8650985. Taken together, our results show that Gem and Brm act antagonistically to modulate the EGFR- Ras- MAPK signaling pathway, by affecting Mek levels during Drosophila development. Paper-15194275. Phosphorylation of Yan, a major target of Ras signaling, leads to Crm1-dependent Yan nuclear export, a response that is regulated by Yan polymerization. Paper-10773132. Collectively, our study reveals a novel regulatory mechanism of the Ras/ ERK pathway by RSK, which negatively regulates ERK activity by acting as a cytoplasmic anchor in Drosophila. Paper-12062836. Recent genetic and molecular studies have identified a set of protein kinases as components of the Ras cascade and nuclear targets of the cascade, including Yan, Pointed, Jun, and Phyllopod. Paper-232035. We have identified and characterized two genes in Drosophila whose products are required for activated RAS to signal with normal efficiency, but do not appear to effect signaling by activated RAF. Paper-438577. Null alleles of hid recapitulate the antiapoptotic activities of Ras/ MAPK, providing genetic evidence that downregulation of hid is an important mechanism by which Ras promotes survival. Paper-1638352. A recent paper by provides evidence that Ras and Rap1 function in parallel to activate Raf downstream of the Torso receptor tyrosine kinase in Drosophila. Paper-10770021. The pointed gene codes for two related proteins, and we show that one form is a constitutive activator of transcription, while the activity of the other form is stimulated by the Ras1/ MAPK pathway. Paper-126667. The observations support a model in which glia express genes necessary for sensory neuron development, and these genes are potentially under the control of the EGFR/ Ras signaling pathway. Paper-9982987. Drosophila Jun ( D-Jun) is a nuclear component of the receptor tyrosine kinase/ Ras signal transduction pathway which triggers photoreceptor differentiation during eye development. Paper-654749. The effects of Ras1 variants on cone cell formation are modulated by changing the gene dosage at the canoe ( cno) locus, which encodes a cytoplasmic protein with Ras-binding activity. Paper-1108438. The ability of Ras to activate PI(3)K has been established in vitro and by overexpression analysis, but its relevance for normal PI(3)K function in vivo is unknown. Paper-12299894. We found that Ras signaling regulates both the levels and subcellular localization of the cell adhesion molecule DE-cadherin/ Shotgun (Shg) in the differentiating wing epithelium. Paper-12529256. These results suggest that the E(sev)2B protein may act to stimulate the ability of Sos to catalyze p21Ras1 activation by linking sevenless and Sos in a signaling complex. Paper-86642. Here, we show that the repressive effect of the RIR is counteracted by the ability of Src42 to associate, in an RTK-dependent manner, with a conserved region located immediately C-terminal to the RIR. Paper-10782006. We propose that binding to 14-3-3 by Raf is necessary but not sufficient for the activation of Raf and that overexpressed Drosophila 14-3-3 requires Ras1 to activate D-Raf. Paper-1238895. We show that Vein/ Egfr binding activates the Ras pathway in the EMA cells leading to the transcription of the tendon-specific genes, stripe, delilah, and beta1 tubulin. Paper-1202857. During oogenesis, epidermal growth factor receptor signaling through the Ras pathway patterns the somatic follicular epithelium, establishing the dorsoventral asymmetry of eggshell and embryo. Paper-9435907. Hence, control of DRacGAP expression by the EGFR/ Ras pathway is a previously undescribed feedback mechanism modulating the intensity and/or duration of its signalling during Drosophila development. Paper-8513355. We have revisited the Ras/ Rap- Ral connections in Drosophila melanogaster by using iterative two-hybrid screens with these three GTPases as primary baits and a subsequent genetic approach. Paper-9685202. Dpp and Hh control eyeless, teashirt, sine oculis, and dachshund expression, Dpp and Ras control homothorax, and all the signaling pathways affect eyes absent expression. Paper-13640275. The testicular phenotypes were suppressed by heterozygous hypomorphic mutations in the Dras1 and drk genes, indicating cross talk between RacGAP-regulated signaling and that of the Ras pathway. Paper-9050237. These results define a function for corkscrew that is either downstream of Ras1 activation or in a parallel pathway that acts with activated Ras1/ Raf to specify R7 photoreceptor development. Paper-536019. Our results support the idea that localised inactivation of transcriptional repressors such as Cic is a rather general mechanism for regulation of target gene expression by the Ras/Raf pathway. Paper-9385330. Receptor tyrosine kinases (RTKs) transmit signals to the cell nucleus via the MAP kinase ( MAPK) cascade, using specific molecules to link the activated receptors to the MAPK cascade activator, Ras. Paper-1631705. Furthermore, the transformation of nonneuronal cone cells into R7 neurons elicited by constitutively active forms of sevenless, Ras1, Raf, and MAP kinase is relieved in the presence of Jun mutants. Paper-133670. Rap1 was found to link dPDZ-GEF to the MAP kinase pathway; however, Ras was not involved in the regulation of the MAP kinase pathway by dPDZ-GEF and actually had an inhibitory function. Paper-9225361. Maintaining growth by expression of either activated Ras or positive regulators of the class I phosphoinositide 3-kinase ( PI3K) pathway inhibits autophagy and blocks salivary gland cell degradation. Paper-12644486. Signal transduction through the RAS/ mitogen-activated protein kinase ( MAPK) pathway depends on a diverse collection of proteins regulating positively and negatively signaling flow. Paper-12004544. We discovered a secondary signal with a permissive role in this process, namely Vein, a neuregulin-like ligand that stimulates the epidermal growth factor receptor ( EGFR) and Ras signaling. Paper-1490830. Expression of dominant-negative Egfr or Ras induces midline crosses, whereas activation of the Egfr or Ras in the leading cell of the ganglionic branch can induce premature turns away from the midline. Paper-10529661. We also present evidence that 14-3-3 epsilon and 14-3-3 zeta, two 14-3-3 protein family members, are partially redundant for RAS1 signaling in photoreceptor formation and in animal viability. Paper-1019063. Here, we report that down-regulation of Egfr/ Ras pathway is critical for haltere fate specification: over-expression of positive components of this pathway causes significant haltere-to-wing transformations. Paper-12176473. While Decapentaplegic ( Dpp) acts downstream of Ras to maintain vein cell identity in the pupal wing, our results indicate that Ras controls Shg localization via a Dpp-independent mechanism. Paper-12529256. Moreover, we show in vivo during wing development and biochemically that Brm acts to promote EGFR- Ras- MAPK signaling, as indicated by its effects on pERK levels, while Gem opposes this. Paper-15194275. In addition, ectopic activation of the Ras/ MAPK pathway in the developing embryo and in the developing eye suppresses naturally occurring apoptosis and regulates the transcription of the proapoptotic gene hid. Paper-1638352. The suppression of abnormal proliferation by the hml-Gal4 construct was not restricted to ytr-deficient hemocytes, but was also observed in hemocytes expressing the oncogenic forms of Raf or Ras proteins. Paper-10609009. The activation of a Ras protein, p21Ras1, is a crucial early event in the signaling pathway, and constitutive activation of p21Ras1 is sufficient to induce all of the effects of sevenless action. Paper-86642. Mitogen-activated protein kinase ( MAPK) activity is increased in Nf1 mutants, and the circadian phenotype is rescued by loss-of-function mutations in the Ras/ MAPK pathway. Paper-9068046. Tor activity elicits the transcription of two 'gap' genes, tailless ( tll) and huckebein ( hkb), in overlapping but distinct domains by stimulating the Ras signal transduction pathway. Paper-1287379. Dmras85D is much more similar to the Ha- ras, Ki- ras, and N-ras genes than it is to either the Dmras64B gene or to the ras genes of Saccharomyces cerevisiae. Paper-5729204. However, although the ectopic proliferation of E1 hypomorphs is dramatically suppressed by removing one copy of Ras, removal of the more upstream components Egfr, Grb2 or sos shows no suppression. Paper-13730953. Our results raise the possibility that neurofibroma formation in individuals with neurofibromatosis might result in part from a Ras- PI3K- Akt-dependent inhibition of FOXO within Schwann cells. Paper-12402224. Unlike other Ras superfamily members, these proteins lack a signal for prenylation, contain a conserved but distinct effector domain, and, in the case of Rin and RIC, contain calmodulin-binding domains. Paper-10774788. The Rho subfamily of Ras-related small GTPases participates in a variety of cellular events including organization of the actin cytoskeleton and signalling by c-Jun N-terminal kinase and p38 kinase cascades. Paper-1781059. Herein, we show that the N-terminal portion of CNK (CNK(N-term)) strongly cooperates with RAS, whereas CNK(C-term) efficiently blocks RAS- and RAF-dependent signaling when overexpressed in the Drosophila eye. Paper-8348597. During Drosophila development, constitutive membrane binding of C3G, which also occurs during v-crk transformation, results in cell fate changes and overproliferation, mimicking overactivity of the RAS- MAPK pathway. Paper-1722782. Gain- or loss-of-function mutations in Ras1 and MAPK reveal that regulation of synapse structure by this signal transduction pathway is dependent on fasciclin II localization at synaptic boutons. Paper-9418112. We demonstrate that yan can repress transcription and that this repression activity is negatively regulated by the Ras1/ MAPK signal, most likely through direct phosphorylation of yan by MAPK. Paper-126667. While the core RTK/ Ras/ MAPK signaling cassette has been studied extensively, little is known about the nature of the downstream targets of the pathway or how these effectors regulate the specificity of cellular responses. Paper-2125472. Here we show that the proneural proteins trigger, in addition, positive interactions among cells of the cluster that are mediated by the Epidermal growth factor receptor ( EGFR) and the Ras/ Raf pathway. Paper-8682613. Interestingly, although alph gene product does not appear to be essential for viability, its elimination leads to weak but significant developmental defects reminiscent of an overactivated RAS/ MAPK pathway. Paper-12004544. These receptors commonly activate Ras/ Raf/MEK/ MAPK signaling but when overactivated can also induce the JAK/ STAT pathway, originally identified as the signaling cascade downstream of cytokine receptors. Paper-9267974. The effects of activated RIC could be mitigated by a reduction in dosage of several genes in the Drosophila Ras cascade, including Son of sevenless (Sos), Dsor ( MEK), rolled ( MAPK), and Ras itself. Paper-10774788. Our results indicate that tissue-specific modulation of EcR activity by the Ras signaling pathway refines temporal ecdysone signals that regulate FC differentiation and cadherin-mediated epithelial cell shape changes. Paper-13210528. These results provide the first evidence for a requirement of Egf receptor activity in differentiated adult Drosophila neurons and show that a delicate balance of Ras activity is essential for the survival of adult neurons. Paper-9748713. In addition to the ability to bind calmodulin, a number of unique features distinguished RIC from other Ras-like GTPases, including the absence of a signal for prenylation and a distinct effector (G2) domain. Paper-797946. In mutants that produce defective dorsal appendages ( K10, Ras and ectopic decapentaplegic) both cell types are specified and reorganize to occupy their stereotypical locations within the otherwise defective tubes. Paper-10775419. Genetic interactions between various dominant enhancer piracy alleles and mutations in the EGF-R/ RAS signaling pathway indicate that many of these novel phenotypes result from ectopic activation of EGF-R signaling. Paper-133677. Collectively, our findings identify dPDZ-GEF as a novel upstream regulator of various morphogenetic pathways and demonstrate the presence of a novel, Ras-independent mechanism for activating the MAP kinase signaling pathway. Paper-9225361. Ras1 and downstream cytoplasmic kinases, Raf, MEK, and MAPK, comprise an evolutionarily conserved cascade that mediates the transmission of signals from RTKs at the plasma membrane to specific factors in the nucleus. Paper-510248. The Caenorhabditis elegans vulva and the Drosophila eye are two classic paradigms for understanding how Ras and Notch affect cell fates, and how the two pathways work together to control biological pattern. Paper-10804930. A genetic screen for novel components of the Ras/Mitogen- activated protein kinase signaling pathway that interact with the yan gene of Drosophila identifies split ends, a new RNA recognition motif-containing protein. Paper-2125472. Mammalian Ras GTPase-activating protein (GAP), p120 Ras-GAP, has been implicated as both a downregulator and effector of Ras proteins, but its precise role in Ras-mediated signal transduction pathways is unclear. Paper-1767493. Both gain-of-function and dominant-negative mutations of Dsrc41 caused the formation of supernumerary R7-type neurons, suppressible by one-dose reduction of boss, sev, Ras1, or other genes involved in the Sev pathway. Paper-591996. Our findings indicate that the Ras/ Raf/MEK/ MAPK signaling pathway is sufficient to mediate the normal functions of wild-type RTK, whereas the effects of gain-of-function mutant RTK additionally require STAT activation. Paper-9267974. Yan SAM (sterile alpha motif) domain mutations preventing polymerization result in Ras-independent, but Crm1-dependent Yan nuclear export, suggesting that polymerization prevents Yan export. Paper-10773132. These data suggest that photoreceptors other than R7 use a Ras1 signalling pathway activated by the spitz/ Egfr interaction, in a manner analogous to the Ras1 pathway activated by boss/sevenless in photoreceptor R7. Paper-155985. RESULTS: Here, we show that the expression of activated Ras, PI3 kinase ( PI3K), or Raf specifically in the PG reduces body size, whereas activated Ras or PI3K, but not Raf, increases PG cell size. Paper-11528747. Instead, levels of Ras activity which suffice to drive tll and hkb transcription at the posterior pole fail to drive their expression in more central portions of the body, apparently due to repression by other gap gene products. Paper-1287379. Therefore, change in tetraspanin Tsp68C expression has a strong suppressor effect on abnormal proliferation and differentiation of hemocytes in the context of specific lesions, such as overactivation of the Ras/Raf/MAPK pathway. Paper-10609009. To investigate the importance of Ras- mediated PI(3)K activation for normal PI(3)K function, we replaced Dp110 with Dp110(RBD), which is unable to bind to Ras but otherwise biochemically normal. Paper-12299894. We demonstrate here that Drosophila tissues containing hypomorphic mutations in E1, the most upstream enzyme in the ubiquitin pathway, display cell-autonomous upregulation of Ras-ERK activity and Ras-dependent ectopic proliferation. Paper-13730953. These two RAS effector loop mutants, however, retain some activity and can act synergistically with a MAPK gain-of-function mutation, suggesting that RAS1 may also act through signaling pathway(s) distinct from the MAPK cascade. Paper-1300985. We conclude that the activation of the Ras cascade may be an important in vivo requisite to the transduction of signals through RIC and that the binding of calmodulin to RIC may negatively regulate this small GTPase. Paper-10774788. In an effort to identify new genes functioning downstream in the Ras/ MAPK/ yan pathway, we have performed a genetic screen to isolate dominant modifiers of the rough eye phenotype associated with eye-specific expression of yan(ACT). Paper-2125472. Together, these findings suggest that CNK is a novel component of a RAS-dependent signaling pathway that regulates RAF function and/or targets RAF to a specific subcellular compartment upon RAS activation. Paper-1638354. These results suggest that over-expressed Dsrc may function through Ras1 to stimulate differentiation in the embryonic nervous system and eye imaginal disc, and that kinase-active Dsrc interferes with these processes. Paper-7669871. We found that the activation of Ras within the PG induces precocious ecdysone release, whereas expression of either dn- PI3K or dn- Raf in the PG greatly attenuates the [ecdysone] increase that causes growth cessation and pupariation onset. Paper-11528747. Targeted disruption of D-Rap1 expression decreased both Torso-dependent ERK activation and the ERK-dependent expression of the zygotic genes tailless and huckebein to levels similar to those achieved in D-Ras1 null embryos. Paper-10804786. Here, we investigate the patterns of expression of activators of EGFR- Ras signalling, as well as some of the effectors, in order to better understand the patterning of the distal leg, and to investigate further roles of this signalling pathway. Paper-11154912. In Drosophila, Drk, an SH2 adaptor protein, Sos, a putative activator of Ras1, Ras1, raf and rolled/MAP kinase have been shown to be required for signalling from the sevenless and the torso receptor tyrosine kinase. Paper-118260. Mutation of the single consensus MAPK phosphorylation site in the second form abrogates this responsiveness. yan is a negative regulator of photoreceptor determination, and genetic data suggest that it acts as an antagonist of Ras1. Paper-126667. This bimodal property depends on the N-terminal region of CNK, which integrates RAS activity to stimulate RAF and a bipartite element, called the RAF-inhibitory region (RIR), which binds and inhibits RAF catalytic activity. Paper-10782006. Furthermore, two RAS effector loop mutations (E37G and Y40C) that block the RAS- RAF interaction, also suppress RAS1V12-induced proliferation, consistent with a requirement for the MAPK cascade during the RAS1 mitogenic response. Paper-1300985. These results suggest that the stimulation of ras protein activity is a key element in the signaling by sevenless and Ellipse and that this stimulation may be achieved by activating the exchange of GTP for bound GDP by the ras protein. Paper-46238. Our genetic analysis demonstrates that DOS functions upstream of Ras1 and defines a signaling pathway that is independent of direct binding of the DRK SH2/ SH3 adaptor protein to the SEV receptor tyrosine kinase. Paper-589407. Our data suggest that yan functions as a cell-autonomous negative regulator of photoreceptor development; in the presumptive R7 and cone cells, yan appears to act antagonistically to the proneural signal mediated by sevenless and Ras1. Paper-7448104. These results on signaling between squamous and columnar epithelia are particularly significant in the context of in vitro studies using human cell lines that suggest a role for the Egfr/ Ras pathway in metastasis and tumour progression. Paper-9964343. Together, this work identifies a PP2C of the alpha/beta subfamily as a novel negative regulator of the RAS/ MAPK pathway and suggests that these evolutionarily conserved enzymes play a similar role in other metazoans. Paper-12004544. We show that the prospero gene becomes transcriptionally activated at a low level in all Sevenless-competent cells prior to Sevenless signaling, and this requires the activities of Ras1 and two Ras1/MAP kinase-responsive ETS transcription factors. Paper-698906. We demonstrate that Wingless ( Wg) and Decapentaplegic ( Dpp) confer competence for receptor tyrosine kinase- mediated induction of a subset of Drosophila muscle and cardiac progenitors by acting both upstream of and in parallel to Ras. Paper-8650985. Here we present genetic evidence suggesting that PP2A functions downstream of Ras1 in the Sevenless receptor tyrosine kinase (RTK) signal transduction pathway that specifies R7 photoreceptor cell fate in the developing Drosophila eye. Paper-510248. We demonstrate that the adapter protein DRK (downstream of receptor kinase) which is essential for signaling to RAS in developmental contexts, is preferentially distributed in the adult mushroom bodies, centers for olfactory learning and memory. Paper-13633259. Participation of RAS, RAF, and mitogen-activated protein kinase ( MAPK) in learning and memory has been demonstrated in a number of studies, but the molecular events requisite for cascade activation and regulation have not been explored. Paper-13633259. The functional interaction between DMKP-3 and the Ras/ DERK pathway was further confirmed by genetic interactions between DMKP-3 loss-of- function mutants or overexpressing transgenic flies and various mutants of the Ras/ DERK pathway. Paper-10215641. During Spitz EGF-mediated neuronal induction in the Drosophila compound eye and chordotonal organs, Spitz causes activation of Ras signaling in the induced cells, resulting in the activation of Ets transcription factor Pointed P2. Paper-9971781. The role of Star in cell-cell signaling is supported by the observation of genetic interactions between Star and mutations that reduce signaling through both sevenless and the Drosophila EGF-receptor homologue, including Ras1 and Son of sevenless. Paper-7615486. These results suggest that Ras may only affect PI3K signaling when mutationally activated, such as in Ras(V12)-transformed cells, and provide a basis for understanding the synergy between Ras and other growth-promoting oncogenes in cancer. Paper-9543689. Here we show that in Drosophila, the receptor tyrosine kinase Torso activates both STAT and Ras during the early phase of PGC development, and coactivation of STAT and Ras is required for PGC proliferation and invasive migration. Paper-10159054. Although p90 ribosomal S6 kinase ( RSK) is known as an important downstream effector of the ribosomal protein S6 kinase/extracellular signal-regulated kinase ( Ras/ ERK) pathway, its endogenous role, and precise molecular function remain unclear. Paper-12062836. Here we show, by analysis of Drosophila mutants, that synaptic current and modulation of K+ current, triggered by a pituitary adenylyl cyclase-activating polypeptide-like neuropeptide, are mediated by coactivation of the Ras/ Raf and Rutabaga-adenylyl cyclase pathways. Paper-266863. Neurofibromatosis type 1 (NF1) is among the most common genetic disorders of humans and is caused by loss of neurofibromin, a large and highly conserved protein whose only known function is to serve as a GTPase-Activating Protein (GAP) for Ras. Paper-12349841. Immunohistochemical staining revealed a circadian oscillation of phospho- MAPK in the vicinity of nerve terminals containing pigment-dispersing factor (PDF), a secreted output from clock cells, suggesting a coupling of PDF to Ras/ MAPK signaling. Paper-9068046. Genetic mosaic studies establish that expression of the retinal determination genes eyeless, teashirt, homothorax, eyes absent, sine oculis, and dachshund are each regulated by combinations of Dpp, Hh, N, Wg, and Ras signals in Drosophila. Paper-13640275. We propose that Ras primarily promotes growth and that growth is coupled to G1/ S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit. Paper-2128408. In contrast, expression of either dominant-negative (dn) Ras, Raf, or PI3K increases body size and prolongs the larval stages, leading to delayed pupariation, whereas expression of dn- PI3K, but not of dn- Raf or dn- Ras, reduces PG cell size. Paper-11528747. We report here that Ras1 activation may account for all of the signalling action of Sev; an activated Ras1Va112 protein rescues the normal R7 precursor from transformation into a cone cell in sev and boss null mutants and induces the formation of supernumerary R7 cells. Paper-52863. Ectopic expression of phyl in the cone cell precursors mimics the effect of ectopic activation of Ras1, suggesting that phyl expression is regulated by Ras1. phyl is also required for embryonic nervous system and sensory bristle development. Paper-165984. We identify a novel growth factor stimulated adenylyl cyclase ( AC) pathway in the Drosophila brain, which is disrupted by mutations in the epidermal growth factor receptor ( EGFR), neurofibromin ( NF1) and Ras, but not Galpha(s). Paper-11329244. We conclude that tll and hkb transcription, as well as the terminal structures, are specified by two inputs: a gradient of Ras activity which emanates from the pole, and the opposing influence of more centrally deployed gap genes which repress the response to Ras. Paper-1287379. D14-3-3 zeta mutant analysis combined with rescue experiments involving gain-of- function alleles of Raf and Ras indicate that D14-3-3 zeta is an essential component of the Raf/ Ras signaling pathway and necessary for photoreceptor differentiation. Paper-1019064. However, in cooperation with oncogenic activated Ras or Notch signalling, JNK becomes an essential driver of tumour overgrowth and invasion. aPKC-dependent signalling in scrib mutants cooperates with JNK to significantly enhance oncogene-mediated tumour overgrowth. Paper-14043901. Clonal analysis and conditional mutant studies establish that roadkill transcription is activated by the EGF receptor and Ras pathway in most differentiating retinal cells, and by both EGF receptor/ Ras and by Hedgehog signaling in cells that remain unspecified. Paper-14077664. This result is supported by analysis of D-Raf activation in the absence of either the exchange factor Son of sevenless (Sos) or the adaptor protein drk ( Grb2), as well as by the phenotype of a D-Raf mutation that abolishes binding of Ras1 to D-Raf. Paper-209497. Recent studies of Drosophila and mammalian cells demonstrate that the TSC1- TSC2 complex functions as GTPase activating protein against Rheb - a Ras-like small GTPase, which in turn regulates TOR signaling in nutrient-stimulated cell growth. Paper-10550956. Later, in a second wave of signalling when all the proximal-distal leg fates have been specified, domains of EGFR/ Ras activation appear inside each leg segment to regulate Notch-mediated joint development, and also some organs such as tendons and sensory organs. Paper-11154912. Furthermore, mitogen-activated protein kinase ( MAPK) phosphorylated Mblk-1 at Ser-444 in vitro, and the Mblk-1- induced transactivation was stimulated by phosphorylation of Ser-444 by the Ras/ MAPK pathway in the luciferase assay. Paper-9708302. The transcription patterns of Drosophila melanogaster src, abl and two ras homologs were analyzed in normal Drosophila tissue, in neuroblasts derived from tumorous larval brain of the mutant lethal(2)giant larvae [ l(2)gl] and in Schneider 2 tissue culture cells. Paper-6145302. Using chromosomal loss-of-function mutations and transgenes encoding dominant-negative and constitutively active proteins, we show that this nonautonomous effect of Ras(V12) is mediated by the Ras effector phosphatidylinositol 3-kinase ( PI3K) and its downstream kinase Akt. Paper-12402224. Furthermore, although yan mutations dominantly interact with mutations in the Ras1, Draf, Dsor1, and rolled ( rl) genes to influence R7 cell development, ttk mutations only interact with yan and rl gene mutations to affect this signaling pathway. Paper-559482. These findings provide the first in vivo evidence that membrane localization of C3G can trigger activation of RAP1 and RAS resulting in the activation of MAPK, one of the hallmarks of v-crk transformation previously thought to be mediated through activation of SOS. Paper-1722782. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR, spitz ( spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. Paper-8931148. Mitogen-activated protein kinase ( MAPK) phosphatase 3 ( MKP-3) is a well-known negative regulator in the Ras/ extracellular signal-regulated kinase (ERK)-MAPK signaling pathway responsible for cell fate determination and proliferation during development. Paper-10215641. We show that (i) the Ral-centered protein network appears to be extremely conserved in human and flies, (ii) in this network, RGL is a functional Drosophila orthologue of RalGEFs, and (iii) the RGL- Ral pathway functionally interacts with both the Ras and Rap pathways. Paper-9685202. We further provide evidence that the E(sev)2B protein is required for activation of p21Ras1 but not for any subsequent events, and that this protein can bind in vitro to sevenless and to Son of sevenless (Sos), a putative guanine nucleotide exchange factor for p21Ras1. Paper-86642. Here, we demonstrated that Drosophila MKP-3 ( DMKP-3) is critically involved in cell differentiation, proliferation, and gene expression by suppressing the Ras/ DERK pathway, specifically binding to DERK via the N-terminal ERK- binding domain of DMKP-3. Paper-10215641. Consistent with the notion that these RTKs share a common signaling pathway, constructs containing the activated downstream elements Dras1 and Draf were also able to rescue tracheal migration, demonstrating that these two proteins are key players in the DFGF-R1 signaling pathway. Paper-8002543. Sequential activation of the intermediates in the Ras/ Raf serine-threonine protein kinase/ MAPK kinase/ MAPK/transcription factor pathway has emerged as a central mechanism for controlling cell proliferation and differentiation in yeast, worms, fruitflies and mammals. Paper-266863. Here we show that upregulation of Ras activity in adult Drosophila neurons induces neuronal cell death, as evident from the phenotype of vacuolar peduncle ( vap) mutants defective in the Drosophila RasGAP gene, which encodes a Ras GTPase-activating protein. Paper-9748713. We demonstrate that maintaining sufficient E1 function is required both cell autonomously and non-cell autonomously to prevent inappropriate Ras-ERK-dependent growth and proliferation in vivo and may implicate loss of Ras ubiquitylation in developmental disorders and cancer. Paper-13730953. In addition, the cone cell to R7 photoreceptor transformation caused by ectopic activation of the Ras pathway during eye development is suppressed by the removal of one functional copy of the dTFIIA-S locus revealing the sensitivity of this process to reductions in dTFIIA-S activity. Paper-470547. Using forced expression of a constitutively active form of Ras1, three developmental potentials (rough, seven-up, and prospero expression) were visualized as relatively narrow bands corresponding to regions where rough-, seven-up- or prospero-expressing ommatidial cells would normally form. Paper-10708231. Our study demonstrates that the Drosophila p21ras, encoded by Ras1, is an intrinsic component of the tor signaling pathway, where it is both necessary and sufficient in specifying posterior terminal cell fates. p21ras/ Ras1 operates upstream of the D-raf kinase in this signaling pathway. Paper-86563. We found that cooperation between oncogenic RasV12 expression and inactivation of any one of a number of genes affecting cell polarity leads to metastatic behavior, including basement membrane degradation, loss of E-cadherin expression, migration, invasion, and secondary tumor formation. Paper-10149995. The study of relationships between emc and different genes involved in wing development reveal strong genetic interactions with genes of the Ras signalling pathway (torpedo, vein, veinlet and Gap), blistered, plexus and net, in both adult wing phenotypes and cell behaviour in genetic mosaics. Paper-1851251. RnRacGAP and Ras cross talk also operated during retinal differentiation; however, while the heterozygous hypomorphic drk mutation continued to act as a suppressor of the rn null mutation, the heterozygous hypomorphic Dras1 mutation induced novel retinal phenotypes. Paper-9050237. Confocal analyses of mosaic egg chambers demonstrate that Ras is required both cell- and non cell-autonomously for morphogenetic behaviors characteristic of dorsal follicle cell migration, and reveal a novel, Ras-dependent pattern of basal E-cadherin localization in dorsal midline follicle cells. Paper-9435907. These results suggest that the ability of Cyclin D/ Cdk4 to drive growth in the proliferating wing cells is distinct from that in the none-dividing eye cells or the ability of activated Ras to induce growth, and that RBF may have a role in regulating growth in the proliferating wing discs. Paper-9395238. Here we report that the Drosophila NF1 growth defect reflects a non-cell-autonomous requirement for NF1 in larval neurons that express the R- Ras ortholog Ras2, that NF1 is a GAP for Ras1 and Ras2, and that a functional NF1-GAP catalytic domain is both necessary and sufficient for rescue. Paper-12349841. Ras induces Notch, its ligand Delta, and the epidermal growth factor receptor antagonist, Argos. We show that Delta and Argos then synergize to nonautonomously block a positive autoregulatory feedback loop that amplifies a fate- inducing Ras signal. Paper-9428961. Here, we show that the scaffold KSR (kinase suppressor of RAS), a RAF homolog known to assemble RAF/ MEK/ ERK complexes, induces RAF activation in Drosophila by a mechanism mediated by its kinase-like domain, but which is independent of its scaffolding property or putative kinase activity. Paper-11372851. Here, we present evidence that the striped pattern of the secreted factor Hedgehog (Hh), in combination with the RAS pathway, specifies and positions neighboring groups of cardiac progenitors within each segment: the anterior ladybird ( lbe)- and the posterior even skipped (eve)-expressing cardiac progenitors. Paper-11376357. Using transgenic flies expressing constitutively activated Ras1 or Raf proteins that function independently of upstream signaling events, we show that a reduction in the dose of the gene encoding the catalytic subunit of PP2A stimulates signaling from Ras1 but impairs signaling from Raf. Paper-510248. Ras1-dependent expression of ommatidial marker genes was regulated by a combinatorial expression of eye prepattern genes such as lozenge, dachshund, eyes absent, and cubitus interruptus, indicating that developmental potential formation is governed by region-specific prepattern gene expression. Paper-10708231. Our results show that loss of NF1 can give rise to non-cell-autonomous developmental defects, implicate aberrant Ras-mediated signaling in larval neurons as the primary cause of the NF1 growth deficiency, and argue against the notion that neurofibromin has separable Ras- and cAMP-related functions. Paper-12349841. Comparison of the Dmras85D genomic sequences with the previously published nucleotide sequence (Neuman-Silberberg et al., Cell 37 (1984) 1027-1033) shows that the positions of the two introns are not conserved relative to the positions of the introns in Dmras64B or in vertebrate ras genes. Paper-5729204. A drastic increase in the number of circulating hemocytes is caused by receptor tyrosine kinases, such as Egfr, Pvr, and Alk, as well as by the downstream signaling components Ras85D and pointed, supporting the notion that the Ras-mitogen-activated protein kinase pathway regulates hemocyte numbers. Paper-10640336. In addition to molecules previously identified from vertebrate studies, i.e. Grb2, Sos, Ras- Gap, p21ras, Raf, MEK and MAPK, genetic studies have suggested that two novel proteins, the protein tyrosine phosphatase (PTPase) Csw and the transmembrane protein Rho, are involved in RPTK signalling. Paper-125974. A screen for mutations that modify a ksr-dependent phenotype identified a novel gene, connector enhancer of ksr (cnk), that functions upstream or in parallel to RAF in the RAS pathway. cnk encodes a protein containing several protein-protein interaction domains, suggesting that it brings different signaling molecules together. Paper-1638354. This leads to defects in early steps of pattern formation and cell fate determination. rux is suppressed by mutations in genes that promote cell cycle progression (i.e., cyclin A and string) and enhanced by mutations in genes that promote differentiation (i.e., Ras1 and Star). rux encodes a novel protein of 335 amino acids. Paper-125307. Extra outer photoreceptor formation was suppressed and enhanced, respectively, by reducing the activity of Ras/ MAPK signaling and by dosage reduction of yan, a negative regulator of the pathway, suggesting interactions between Bar homeobox genes (cell fate determinants) and Ras/ MAPK signaling in eye development. Paper-1558829. During specification of muscle and cardiac progenitors from clusters of equivalent cells in the Drosophila embryonic mesoderm, the Ras/ MAPK pathway--activated by both epidermal and fibroblast growth factor receptors--functions as an inductive cellular determination signal, while lateral inhibition mediated by Notch antagonizes this activity. Paper-9428961. A genetic screen for dominant enhancers and suppressors of this phenotype identified mutations in a number of genes required for normal eye development, including UbcD1, which encodes a ubiquitin conjugating enzyme; SR3-4a, a gene previously implicated in signaling downstream of Ras1; and a Drosophila homolog of the Sin3A transcriptional repressor. Paper-1353907. Here we isolated Drosophila melanogaster PDZ-GEF ( dPDZ-GEF), which contains the all-conserved domains of mammalian and nematode PDZ-GEF including cyclic nucleotide monophosphate-binding, Ras exchange motif, PDZ, RA, and GEF domains. dPDZ-GEF loss-of-function mutants were defective in the development of various organs including eye, wing, and ovary. Paper-9225361. In addition to regulating the expression of proximal Ras pathway components, Wg and Dpp coordinate the direct effects of three signal-activated ( dTCF, Mad, and Pointed- functioning in the Wg, Dpp, and Ras/ MAPK pathways, respectively) and two tissue-restricted ( Twist and Tinman) transcription factors on a progenitor identity gene enhancer. Paper-8650985. These synonyms are used for gene Ras85D (Ras oncogene at 85D): Su(tor)3-2, S35097, RTK, RasV12, Ras-like protein 1, RasI, RAS85D, ras85D, ras85B, Ras1/RAs85D, Ras-1, ras 1, RAS1, Ras1, ras1, Ras[V12], RAS, Ras, ras, p21[Ras1], l(3)s1747, l(3)06677, fs(3)05703, EK3-4, E(sev)3C, E(faf), DRas85D/Ras, Dras85D, dRas85D, D-ras-1, D-Ras1, D-ras1, DRAS1, Dras1, dRAS1, dRas1, dras1, D-Ras, DRas, Dras, dRas, Dmras85D, Dm Ras1, Dmel\CG9375, C-ras1, CG9375. These accession numbers are used for gene Ras85D: Q9V448 (UNIPROT__AC), CAA51689 (NCBI_GENBANK__AC), AAF54388 (NCBI_GENBANK__AC). Ras85D is a homologue of let-60 (LEThal) from Caenorhabditis elegans. Ras85D is a homologue of KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Homo sapiens. Ras85D is a homologue of KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Pan troglodytes. Ras85D is a homologue of KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Canis lupus familiaris. Ras85D is a homologue of KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Bos taurus. Ras85D is a homologue of KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Gallus gallus. Ras85D is a homologue of Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Mus musculus. Ras85D is a homologue of Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Rattus norvegicus. Ras85D is a homologue of kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) from Danio rerio. Ras85D is a homologue of AgaP_AGAP002219 (AGAP002219-PA) from Anopheles gambiae str. PEST. Important links ! iHOP - Information Hyperlinked over Proteins . Concept & Implementation by Robert Hoffmann.