The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Gerald M. Rubin - One of the best experts on this subject based on the ideXlab platform.
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phyl acts to down regulate ttk88 a transcriptional repressor of neuronal cell fates by a sina dependent mechanism
Cell, 1997Co-Authors: Amy H Tang, Thomas P Neufeld, Elaine Kwan, Gerald M. RubinAbstract:Abstract We show that Tramtrack (TTK88) expression represses neuronal fate determination in the developing Drosophila eye. Phyllopod (PHYL) acts to antagonize this repression by a mechanism that requires Seven In Absentia (SINA) and is associated with decreased TTK88 protein levels, but not reduced ttk88 gene transcription or mRNA stability. We present evidence that SINA, PHYL, and TTK88 physically interact and that SINA interacts genetically and physically with UBCD1, a component of the ubiquitin-dependent protein degradation pathway. Our results suggest a model in which activation of the Sevenless receptor tyrosine kinase induces PHYL expression, which then acts with SINA to target the transcriptional repressor TTK88 for degradation, thereby promoting R7 cell fate specification.
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sev Sevenless receptor ptk d melanogaster
The Protein Kinase FactsBook#R##N#Protein-Serine Kinases, 1995Co-Authors: Gerald M. RubinAbstract:The Sevenless receptor protein-tyrosine kinase functions during development of the Drosophila melanogaster(D. melanogaster) compound eye, where its activity is required to specify the identity of one particular class of photoreceptor, the R7 cell. Sev is first synthesized as a glycoprotein precursor that is subsequently cleaved into 220-kDa (N-terminal) and 58-kDa subunits that remain associated by noncovalent interactions. p220 is glycosylated and contains most of the extracellular portion of the protein, and p58 is composed of a small portion of the extracellular sequences, a transmembrane domain, and the intracellular kinase domain. A second putative transmembrane domain is in the 220-kDa subunit, but it is unclear if this serves as an N-terminal anchor or as a cleaved signal sequence. The size of the protein, as estimated by gel filtration, suggests that it may exist as an α2/β2 dimer. Sev is expressed on the apical surface of many cells in the developing D. melanogaster retina, in a highly dynamic pattern that is controlled at the level of transcription of the Sevenless gene. No other sites of high-level expression have been identified, although the protein has been detected in protein immunoblots of adult extracts.
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mutations in hsp83 and cdc37 impair signaling by the Sevenless receptor tyrosine kinase in drosophila
Cell, 1994Co-Authors: Tyler Cutforth, Gerald M. RubinAbstract:Abstract A highly conserved signal cascade functions subsequent to receptor tyrosine kinase activation. Signaling by the Sevenless receptor, required for differentiation of the R7 photoreceptor neuron in Drosophila, is reduced by mutations in E(sev)3A and E(sev)3B . We show here that E(sev)3A is a member of the Hsp90 family of stress proteins and that E(sev)3B encodes a homolog of the cell cycle control protein Cdc37 from S. cerevisiae. Mutations in E(sev)3B also dominantly enhance mutations in Dmcdc2 , the gene encoding the p34 protein kinase that regulates the G2/M transition. Together, these data support a role for Hsp90 proteins in tyrosine kinase regulation and suggest that signals promoting neuronal differentiation may involve cell cycle control.
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the interaction of bride of Sevenless with Sevenless is conserved between drosophila virilis and drosophila melanogaster
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: A C Hart, Gerald M. Rubin, D Van Vactor, S D Harrison, S L ZipurskyAbstract:Abstract An inductive interaction between the Sevenless (sev) transmembrane tyrosine kinase receptor and the bride of Sevenless (boss) transmembrane ligand is required for the development of the R7 photoreceptor neuron in the compound eye of Drosophila melanogaster. The boss protein is proposed to contain a large N-terminal extracellular domain, seven transmembrane segments, and a C-terminal cytoplasmic tail. The boss protein from Drosophila virilis (bossvir) retains strong amino acid identity with loss from D. melanogaster (bossmel): 73% identity in the N-terminal extracellular domain and 91% identity in the seven-transmembrane domain, including the cytoplasmic tail. By using P-element-mediated DNA transformation, the bossmel and bossvir genes were shown to rescue the D. melanogaster boss1 mutation. The expression of bossvir protein in D. melanogaster is indistinguishable from that of bossmel protein. Noncoding sequences which may regulate boss expression were identified based on their conservation during evolution. The predicted sev protein from D. virilis (sevvir) was previously shown to be 63% identical to sev from D. melanogaster (sevmel). A chimeric gene, (sevvir/mel), encoding the extracellular domain of sevvir and the cytoplasmic domain of sevmel rescues the D. melanogaster sevd2 mutation through interaction with either bossvir or bossmel.
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negative control of photoreceptor development in drosophila by the product of the yan gene an ets domain protein
Cell, 1992Co-Authors: Gerald M. RubinAbstract:Abstract Loss-of-function mutations in the yan gene result in the differentiation of supernumerary photoreceptors in the Drosophila eye. The yan gene encodes a protein with an ETS DNA-binding domain that accumulates in the nuclei of undifferentiated cells during the early stages of eye development. 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.
Ernst Hafen - One of the best experts on this subject based on the ideXlab platform.
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socs36e specifically interferes with Sevenless signaling during drosophila eye development
Developmental Biology, 2009Co-Authors: Isabel Almudi, Ernst Hafen, Montserrat Corominas, Hugo Stocker, Florenci SerrasAbstract:During the development of multicellular organisms the fate of individual cells is specified with great precision and reproducibility. Although classical genetic approaches led to the identification of many of the signaling pathways contributing to cell fate specification, they have provided little insight into the mechanisms that ensure robustness and reproducibility. We have used the specification of the R7 photoreceptor cells controlled by the Sevenless receptor tyrosine kinase (Sev) pathway to screen for modulators of pathway activity and to uncover the mechanisms underlying the robustness of cell fate decisions. Here we provide genetic evidence that the Drosophila SOCS36E adaptor protein containing an SH2 domain and a SOCS box acts as an attenuator of Sev signaling. Overexpression of Socs36E strongly suppresses the specification of extra R7 photoreceptor cells in response to constitutive activation of Sev, and loss of Socs36E function suppresses the loss of R7 cells when Sev activity is impaired. In a wild-type background, however, loss and gain of Socs36E function exhibits little effect on R7 specification. We also show that SH2 domain of SOCS36E is essential for this function in inhibiting Sev action and that Socs36E expression is suppressed by high Sev pathway activity. In our model, only the cell able to activate high levels of receptor tyrosine kinase signaling will repress SOCS36E expression, reduce the negative effect on Sev signaling and allow this cell to differentiate into R7. In contrast, the remaining cells fail to receive high signaling, and thus maintain high levels of SOCS36E. This represses residual Sev activity and blocks R7 development. Therefore, Socs36E constitutes a novel partially redundant feedback mechanism that contributes to the robustness of R7 specification. The SOCS family of adaptor proteins may have evolved as modulators of specific signaling pathways that contribute to the robustness and precision of cell fate specification.
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the cdi tesk1 kinase is required for Sevenless signaling and epithelial organization in the drosophila eye
Journal of Cell Science, 2006Co-Authors: Marta Sese, Ernst Hafen, Montserrat Corominas, Hugo Stocker, Tapio I Heino, Florenci SerrasAbstract:How cellular behaviors such as cell-to-cell communication, epithelial organization and cell shape reorganization are coordinated during development is poorly understood. The developing Drosophila eye offers an ideal model system to study these processes. Localized actin polymerization is required to constrict the apical surface of epithelial cells of the eye imaginal disc to maintain the refined arrangement of the developing ommatidia. The identity of each photoreceptor cell within the epithelium is determined by cell-to-cell contacts involving signal transduction events. The R7 photoreceptor cell requires the activity of the Sevenless RTK to adopt a proper cell fate. We performed an EP screen for negative regulators of this inductive process, and we identified the serine/threonine kinase Center divider (cdi) as a suppressor of the phenotype caused by an activated Sevenless receptor. Cdi is homologous to the human testis-specific kinase 1 (TESK1), a member of the LIM kinases involved in cytoskeleton control through ADF/cofilin phosphorylation. We have analyzed the effects of gain- and loss-of-function of cdi and found alterations in actin organization and in the adherens junctions proteins DE-cadherin and β-catenin, as well as in Sevenless apical localization. Interference with the function of the ADF/cofilin phosphatase Slingshot (ssh), which antagonizes Cdi, also results in a suppression of signaling triggered by the Sevenless RTK. Our results reveal a critical interplay between the localization of molecules involved in epithelial organization and signal transduction.
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The Cdi/TESK1 kinase is required for Sevenless signaling and epithelial organization in the Drosophila eye
Journal of Cell Science, 2006Co-Authors: Marta Sese, Ernst Hafen, Montserrat Corominas, Hugo Stocker, Tapio I Heino, Florenci SerrasAbstract:How cellular behaviors such as cell-to-cell communication, epithelial organization and cell shape reorganization are coordinated during development is poorly understood. The developing Drosophila eye offers an ideal model system to study these processes. Localized actin polymerization is required to constrict the apical surface of epithelial cells of the eye imaginal disc to maintain the refined arrangement of the developing ommatidia. The identity of each photoreceptor cell within the epithelium is determined by cell-to-cell contacts involving signal transduction events. The R7 photoreceptor cell requires the activity of the Sevenless RTK to adopt a proper cell fate. We performed an EP screen for negative regulators of this inductive process, and we identified the serine/threonine kinase Center divider (cdi) as a suppressor of the phenotype caused by an activated Sevenless receptor. Cdi is homologous to the human testis-specific kinase 1 (TESK1), a member of the LIM kinases involved in cytoskeleton control through ADF/cofilin phosphorylation. We have analyzed the effects of gain- and loss-of-function of cdi and found alterations in actin organization and in the adherens junctions proteins DE-cadherin and β-catenin, as well as in Sevenless apical localization. Interference with the function of the ADF/cofilin phosphatase Slingshot (ssh), which antagonizes Cdi, also results in a suppression of signaling triggered by the Sevenless RTK. Our results reveal a critical interplay between the localization of molecules involved in epithelial organization and signal transduction.
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The Cdi/TESK1 kinase is required for Sevenless signaling and epithelial organization in the Drosophila eye.
Journal of cell science, 2006Co-Authors: Marta Sese, Ernst Hafen, Montserrat Corominas, Hugo Stocker, Tapio I Heino, Florenci SerrasAbstract:How cellular behaviors such as cell-to-cell communication, epithelial organization and cell shape reorganization are coordinated during development is poorly understood. The developing Drosophila eye offers an ideal model system to study these processes. Localized actin polymerization is required to constrict the apical surface of epithelial cells of the eye imaginal disc to maintain the refined arrangement of the developing ommatidia. The identity of each photoreceptor cell within the epithelium is determined by cell-to-cell contacts involving signal transduction events. The R7 photoreceptor cell requires the activity of the Sevenless RTK to adopt a proper cell fate. We performed an EP screen for negative regulators of this inductive process, and we identified the serine/threonine kinase Center divider (cdi) as a suppressor of the phenotype caused by an activated Sevenless receptor. Cdi is homologous to the human testis-specific kinase 1 (TESK1), a member of the LIM kinases involved in cytoskeleton control through ADF/cofilin phosphorylation. We have analyzed the effects of gain- and loss-of-function of cdi and found alterations in actin organization and in the adherens junctions proteins DE-cadherin and beta-catenin, as well as in Sevenless apical localization. Interference with the function of the ADF/cofilin phosphatase Slingshot (ssh), which antagonizes Cdi, also results in a suppression of signaling triggered by the Sevenless RTK. Our results reveal a critical interplay between the localization of molecules involved in epithelial organization and signal transduction.
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dos a novel pleckstrin homology domain containing protein required for signal transduction between Sevenless and ras1 in drosophila
Cell, 1996Co-Authors: Thomas Raabe, Juan Rafael Riesgo Escovar, Burkhard S Bausenwein, Peter Deak, Peter Maroy, Ernst HafenAbstract:The specification of the R7 photoreceptor cell in the developing eye of Drosophila is dependent upon activation of the Sevenless (SEV) receptor tyrosine kinase. By screening for mutations that suppress signaling via a constitutively activated SEV protein, we have identified a novel gene, daughter of Sevenless (dos). DOS is required not only for signal transduction via SEV but also in other receptor tyrosine kinase signaling pathways throughout development. The presence of an amino-terminally located pleckstrin homology domain and many potential tyrosine phosphorylation sites suggests that DOS functions as an adaptor protein able to interact with multiple signaling molecules. 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.
Michael A. Simon - One of the best experts on this subject based on the ideXlab platform.
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mask a large ankyrin repeat and kh domain containing protein involved in drosophila receptor tyrosine kinase signaling
Development, 2002Co-Authors: Rachel K Smith, Pamela M Carroll, John D Allard, Michael A. SimonAbstract:The receptor tyrosine kinases Sevenless (SEV) and the Epidermal growth factor receptor (EGFR) are required for the proper development of the Drosophila eye. 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. In order to identify additional components of these signaling pathways, mutations that enhanced the phenotype of a dominant negative form of Corkscrew were isolated. This genetic screen identified the novel signaling molecule MASK, a large protein that contains two blocks of ankyrin repeats as well as a KH domain. MASK genetically interacts with known components of these RTK signaling pathways. In the developing eye imaginal disc, loss of MASK function generates phenotypes similar to those generated by loss of other components of the SEV and EGFR pathways. These phenotypes include compromised photoreceptor differentiation, cell survival and proliferation. Although MASK is localized predominantly in the cellular cytoplasm, it is not absolutely required for MAPK activation or nuclear translocation. 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.
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recruitment of the protein tyrosine phosphatase csw by dos is an essential step during signaling by the Sevenless receptor tyrosine kinase
The EMBO Journal, 1999Co-Authors: Ronald Herbst, Xiaolong Zhang, Michael A. SimonAbstract:The pleckstrin homology (PH) domain-containing protein Daughter of Sevenless (DOS) is an essential component of the Sevenless receptor tyrosine kinase (SEV) signaling cascade, which specifies R7 photoreceptor development in the Drosophila eye. Previous results have suggested that DOS becomes tyrosine phosphorylated during SEV signaling and collaborates with the protein tyrosine phosphatase CSW. We have investigated this possibility by identifying tyrosine residues 801 and 854 of DOS as the phosphorylated binding sites for the CSW SH2 domains. We show that these sites become phosphorylated in response to SEV activation and that phosphorylation of both sites is required to allow CSW to bind DOS. Mutant DOS proteins in which either Y801 or Y854 of DOS has been changed to phenylalanine are unable to function during signaling by SEV and other receptor tyrosine kinases. In contrast, we find that a mutant DOS protein in which all tyrosine phosphorylation sites except Y801 and Y854 have been removed is able effectively to provide DOS function during SEV signaling and to rescue the lethality associated with dos loss-of-function mutations. These results indicate that a primary role for DOS during signaling by SEV and other receptor tyrosine kinases is to become phosphorylated at Y801 and Y854 and then recruit CSW.
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daughter of Sevenless is a substrate of the phosphotyrosine phosphatase corkscrew and functions during Sevenless signaling
Cell, 1996Co-Authors: Ronald Herbst, Pamela M Carroll, John D Allard, Thomas Raabe, James Schilling, Michael A. SimonAbstract:Abstract The SH2 domain–containing phosphotyrosine phosphatase Corkscrew (CSW) is an essential component of the signaling pathway initiated by the activation of the Sevenless receptor tyrosine kinase (SEV) during Drosophila eye development. We have used genetic and biochemical approaches to identify a substrate for CSW. Expression of a catalytically inactive CSW was used to trap CSW in a complex with a 115 kDa tyrosine-phosphorylated substrate. This substrate was purified and identified as the product of the daughter of Sevenless ( dos ) gene. Mutations of dos were identified in a screen for dominant mutations which enhance the phenotype caused by overexpression of inactive CSW during photoreceptor development. Analysis of dos mutations indicates that DOS is a positive component of the SEV signaling pathway and suggests that DOS dephosphorylation by CSW may be a key event during signaling by SEV.
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the sh2 containing tyrosine phosphatase corkscrew is required during signaling by Sevenless ras1 and raf
Development, 1996Co-Authors: John D Allard, Henry C Chang, Ronald Herbst, Helen Mcneill, Michael A. SimonAbstract:The Sevenless gene encodes a receptor tyrosine kinase which is required for the development of the R7 photoreceptor cell in each ommatidium of the Drosophila eye. We have previously used a sensitized genetic screen to identify mutations, designated Enhancers of Sevenless (E(sev)), which affect genes that encode components of the Sevenless signaling pathway. Here, we report that one of these mutations, E(sev)1A e0P is a dominantly inhibiting allele of corkscrew, which encodes an SH2 domain-containing protein tyrosine phosphatase (Perkins et al., 1992). We show that corkscrew function is essential for Sevenless signaling and that expression of a membrane-targeted form of corkscrew can drive R7 photoreceptor development in the absence of Sevenless function. Furthermore, we have used the dominantly inhibiting corkscrew allele to examine the role of corkscrew during signaling by activated forms of Ras1 and Raf. Our analysis indicates that corkscrew function is still required during signaling by activated Ras1 and Raf proteins. 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. SUMMARY
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an sh3 sh2 sh3 protein is required for p21ras1 activation and binds to Sevenless and sos proteins in vitro
Cell, 1993Co-Authors: Michael A. SimonAbstract:Abstract Activation of the Sevenless protein-tyrosine kinase is required for the proper specification of R7 photoreceptors in the Drosophila eye. The activation of a Ras protein, p21 Ras1 , is a crucial early event in the signaling pathway, and constitutive activation of p21 Ras1 is sufficient to induce all of the effects of Sevenless action. Here we report that another gene, E(sev)2B , required for proper signaling by Sevenless encodes a protein of the structure SH3-SH2-SH3. We further provide evidence that the E(sev)2B protein is required for activation of p21 Ras1 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 p21 Ras1 . These results suggest that the E(sev)2B protein may act to stimulate the ability of Sos to catalyze p21 Ras1 activation by linking Sevenless and Sos in a signaling complex. We have renamed the E(sev)2B locus downstream of receptor kinases (drk) .
Barry J Dickson - One of the best experts on this subject based on the ideXlab platform.
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nuclear factors in Sevenless signalling
Trends in Genetics, 1995Co-Authors: Barry J DicksonAbstract:Recent studies in both vertebrates and invertebrates support an ‘hourglass' model for signal transduction from receptor tyrosine kinases: Ras channels signals from diverse receptor tyrosine kinases into a common cytoplasmic kinase cascade, the targets of which are an even more diverse collection of nuclear proteins. What are these nuclear factors, and how do they interact to direct specific cellular responses to a generic signal? The past year has brought considerable progress in our quest to answer these questions in one model genetic system, the Drosophila eye.
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the drosophila rolled locus encodes a map kinase required in the Sevenless signal transduction pathway
The EMBO Journal, 1994Co-Authors: W H Biggs, Barry J Dickson, E Hafen, Damian Brunner, K H Zavitz, A Van Der Straten, S L ZipurskyAbstract:Abstract Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the Sevenless (Sev) RTK is required for development of the R7 photoreceptor cell. 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. In this report we present evidence that a Drosophila MAP kinase, ERK-A, is encoded by the rolled locus and is required downstream of raf in the Sev signal transduction pathway.
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genetic dissection of signal transduction mediated by the Sevenless receptor tyrosine kinase in drosophila
Progress in Neurobiology, 1994Co-Authors: Ernst Hafen, Barry J Dickson, Damian Brunner, T RaabeAbstract:Abstract The specification of the R7 photoreceptor cell fate in the developing eye of Drosophila depends on the local activation of the Sevenless (sev) receptor tyrosine kinase by boss, a protein expressed on the membrane of the neighboring R8 cell. Constitutive activation of the sev receptor results in a dosage dependent increase in the number of R7 cells per ommatidium. Genetic screens have been used to identify mutations that alter the efficiency of signal transduction. Subsequent molecular characterization of the corresponding genes has led to the identification of a number of proteins involved in transducing the signal from the receptor to the nucleus. In contrast to the receptor and its ligand, these components are shared between different signal transduction pathways not only in Drosophila but are also homologous to components involved in signal transduction in other organisms.
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a drosophila sh2 sh3 adaptor protein implicated in coupling the Sevenless tyrosine kinase to an activator of ras guanine nucleotide exchange sos
Cell, 1993Co-Authors: Jean Paul Olivier, Barry J Dickson, Ernst Hafen, T Raabe, Mark Henkemeyer, Geraldine Mbamalu, Ben Margolis, Joseph Schlessinger, Tony PawsonAbstract:Abstract A Drosophila gene ( drk ) encodes a widely expressed protein with a single SH2 domain and two flanking SH3 domains, which is homologous to the Sem-5 protein of C. elegans and mammalian GRB2. Genetic analysis suggests that drk function is essential for signaling by the Sevenless receptor tyrosine kinase. Drk biological activity correlates with binding of itS SH2 domain to activated receptor tyrosine kinases and concomitant localization of drk to the plasma membrane. In vitro, drk also binds directly to the C-terminal tall of Sos, a Ras guanine nucleotide-releasing protein (GNRP), which, like Ras1 and drk, is required for Sevenless signaling. These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. The conservation of these signaling proteins during evolution indicates that this is a general mechanism for linking tyrosine kinases to Ras.
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raf functions downstream of ras1 in the Sevenless signal transduction pathway
Nature, 1992Co-Authors: Barry J Dickson, Frank Sprenger, Deborah Morrison, Ernst HafenAbstract:SPECIFICATION of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell1–3. Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Rasl, Sos, Gapl and sina (refs 4–8). The Drosophila homologue of the mammalian Raf-1 serine/threonine kinase, which has been implicated in signal transduction pathways activated by many receptor tyrosine kinases (reviewed in refs 9 and 10), is encoded by the raf locus (also known as l(l)polehole11, Draf-112 or Draf13). Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function. We also present genetic evidence suggesting that Raf acts downstream of Rasl and upstream of Sina in this signal transduction cascade.
S L Zipursky - One of the best experts on this subject based on the ideXlab platform.
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the drosophila rolled locus encodes a map kinase required in the Sevenless signal transduction pathway
The EMBO Journal, 1994Co-Authors: W H Biggs, Barry J Dickson, E Hafen, Damian Brunner, K H Zavitz, A Van Der Straten, S L ZipurskyAbstract:Abstract Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the Sevenless (Sev) RTK is required for development of the R7 photoreceptor cell. 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. In this report we present evidence that a Drosophila MAP kinase, ERK-A, is encoded by the rolled locus and is required downstream of raf in the Sev signal transduction pathway.
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the interaction of bride of Sevenless with Sevenless is conserved between drosophila virilis and drosophila melanogaster
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: A C Hart, Gerald M. Rubin, D Van Vactor, S D Harrison, S L ZipurskyAbstract:Abstract An inductive interaction between the Sevenless (sev) transmembrane tyrosine kinase receptor and the bride of Sevenless (boss) transmembrane ligand is required for the development of the R7 photoreceptor neuron in the compound eye of Drosophila melanogaster. The boss protein is proposed to contain a large N-terminal extracellular domain, seven transmembrane segments, and a C-terminal cytoplasmic tail. The boss protein from Drosophila virilis (bossvir) retains strong amino acid identity with loss from D. melanogaster (bossmel): 73% identity in the N-terminal extracellular domain and 91% identity in the seven-transmembrane domain, including the cytoplasmic tail. By using P-element-mediated DNA transformation, the bossmel and bossvir genes were shown to rescue the D. melanogaster boss1 mutation. The expression of bossvir protein in D. melanogaster is indistinguishable from that of bossmel protein. Noncoding sequences which may regulate boss expression were identified based on their conservation during evolution. The predicted sev protein from D. virilis (sevvir) was previously shown to be 63% identical to sev from D. melanogaster (sevmel). A chimeric gene, (sevvir/mel), encoding the extracellular domain of sevvir and the cytoplasmic domain of sevmel rescues the D. melanogaster sevd2 mutation through interaction with either bossvir or bossmel.
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interaction of bride of Sevenless membrane bound ligand and the Sevenless tyrosine kinase receptor
Nature, 1991Co-Authors: Helmut Kramer, Ross L Cagan, S L ZipurskyAbstract:During development of the Drosophila retina, the R8 photoreceptor neuron induces a neighbouring cell to assume an R7 cell fate. Genetic data suggest that the induction is mediated by two transmembrane proteins encoded by bride of Sevenless and Sevenless. A direct interaction between these two proteins was demonstrated by the heterotypic aggregation of cell lines expressing them. In the developing eye the Sevenless-dependent internalization of bride of Sevenless by the R7 precursor cell provides evidence for a direct interaction between these two proteins in vivo.
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induction of cell fate in the drosophila retina the bride of Sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments
Genes & Development, 1990Co-Authors: A C Hart, Helmut Kramer, D Van Vactor, M Paidhungat, S L ZipurskyAbstract:: Previous genetic mosaic studies established that expression of the Drosophila bride of Sevenless (boss) gene is required in photoreceptor neuron R8 for the development of photoreceptor neuron R7. This led to the proposal that boss encodes or regulates an R7-specific inductive cue. We have identified the boss gene based on small deletions in mutant alleles and sequenced both cDNAs and corresponding genomic regions. One P element and three X-ray-induced boss alleles show different deletions in the gene ranging in size from 2 to 23 bp, each causing frameshifts leading to premature termination of translation. The boss gene encodes a protein of 896 amino acids with a putative amino-terminal signal sequence, a large extracellular region of 498 amino acids, and seven potential transmembrane domains followed by a carboxy-terminal cytoplasmic tail of 115 amino acids. The putative membrane localization of the boss protein is consistent with a model in which direct interaction between the boss and Sevenless proteins specifies R7 cell fate. Another model in which the boss protein functions as a receptor is proposed based on its similarity to the G protein-linked family of membrane receptors.