Gene Symbol: drk
Description: downstream of receptor kinase
Alias: 24/1, CG6033, DRK, Dmel\CG6033, Drk, Drk/Grb2, E(sev)2B, GRB2, Grb-2, Grb/drk, Grb2, Grb2/drk, P1112, Su(sev)R1, crkl, l(2)10626, l(2)k13809, downstream of receptor kinase, CG6033-PA, CG6033-PB, CG6033-PC, CG6033-PD, CG6033-PF, downstream of receptor kinases, downstream receptor kinase, drk-PA, drk-PB, drk-PC, drk-PD, drk-PF, enhancer of sevenless-2B
Species: fruit fly

Top Publications

  1. Schweitzer R, Howes R, Smith R, Shilo B, Freeman M. Inhibition of Drosophila EGF receptor activation by the secreted protein Argos. Nature. 1995;376:699-702 pubmed
    ..Thus the determination of cells by the DER pathway is regulated by a balance between extracellular activating and inhibiting signals. This is the first in vivo example of an extracellular inhibitor of a receptor tyrosine kinase. ..
  2. Farrow N, Zhang O, Forman Kay J, Kay L. Characterization of the backbone dynamics of folded and denatured states of an SH3 domain. Biochemistry. 1997;36:2390-402 pubmed
    ..the backbone dynamics of folded and denatured states of the N-terminal SH3 domain from the adapter protein drk, in high salt or guanidinium chloride, respectively...
  3. Diaz Benjumea F, Hafen E. The sevenless signalling cassette mediates Drosophila EGF receptor function during epidermal development. Development. 1994;120:569-78 pubmed
    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...
  4. Raabe T, Riesgo Escovar J, Liu X, Bausenwein B, Deak P, Maroy P, et al. DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila. Cell. 1996;85:911-20 pubmed
    ..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.
  5. Hou X, Chou T, Melnick M, Perrimon N. The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway. Cell. 1995;81:63-71 pubmed
    ..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...
  6. Olivier J, Raabe T, Henkemeyer M, Dickson B, Mbamalu G, Margolis B, et al. A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell. 1993;73:179-91 pubmed
    ..elegans and mammalian GRB2. Genetic analysis suggests that drk function is essential for signaling by the sevenless receptor tyrosine kinase...
  7. Perrimon N. Signalling pathways initiated by receptor protein tyrosine kinases in Drosophila. Curr Opin Cell Biol. 1994;6:260-6 pubmed
    ..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 ..
  8. Hime G, Dhungat M, Ng A, Bowtell D. D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites. Oncogene. 1997;14:2709-19 pubmed
    ..c-Cbl and SLI-1 and consequently is unable to bind SH3-domain containing adaptor proteins, including the Drosophila Grb2 homologue, Drk...
  9. Robertson H, Hime G, Lada H, Bowtell D. A Drosophila analogue of v-Cbl is a dominant-negative oncoprotein in vivo. Oncogene. 2000;19:3299-308 pubmed

More Information


  1. Chang Y, Lin S, Liang S, Pan K, Chou C, Chen C, et al. Tyrosine phosphoproteomics and identification of substrates of protein tyrosine phosphatase dPTP61F in Drosophila S2 cells by mass spectrometry-based substrate trapping strategy. J Proteome Res. 2008;7:1055-66 pubmed publisher
  2. Botella J, Kretzschmar D, Kiermayer C, Feldmann P, Hughes D, Schneuwly S. Deregulation of the Egfr/Ras signaling pathway induces age-related brain degeneration in the Drosophila mutant vap. Mol Biol Cell. 2003;14:241-50 pubmed
    ..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. ..
  3. Smith J, Cummings C, Cronmiller C. Daughterless coordinates somatic cell proliferation, differentiation and germline cyst survival during follicle formation in Drosophila. Development. 2002;129:3255-67 pubmed
    ..Collectively, these da functions govern the abundance and diversity of somatic cells as they coordinate with germline cysts to form functional follicles. ..
  4. Tollinger M, Forman Kay J, Kay L. Measurement of side-chain carboxyl pK(a) values of glutamate and aspartate residues in an unfolded protein by multinuclear NMR spectroscopy. J Am Chem Soc. 2002;124:5714-7 pubmed
    ..The methodology is applied to an (15)N, (13)C labeled sample of the N-terminal SH3 domain of the Drosophila protein drk, which exists in equilibrium between folded (F(exch)) and unfolded (U(exch)) states under nondenaturing conditions...
  5. Cagan R. Cell fate specification in the developing Drosophila retina. Dev Suppl. 1993;:19-28 pubmed
    ..In addition, the role of local cell interactions in directing cell fate is assessed. ..
  6. Almudi I, Corominas M, Serras F. Competition between SOCS36E and Drk modulates Sevenless receptor tyrosine kinase activity. J Cell Sci. 2010;123:3857-62 pubmed publisher
    ..By contrast, downstream of receptor kinase (Drk), the fly homolog of the mammalian Grb2 adaptor protein, which also contains an SH2 domain, acts ..
  7. Karlovich C, Bonfini L, McCollam L, Rogge R, Daga A, Czech M, et al. In vivo functional analysis of the Ras exchange factor son of sevenless. Science. 1995;268:576-9 pubmed
    ..for Ras and interacts with the receptor tyrosine kinase Sevenless through the protein Drk, a homolog of mammalian Grb2. In vivo structure-function analysis revealed that the amino terminus of Sos was essential for its function in ..
  8. Zimmerman E, Palsson A, Gibson G. Quantitative trait loci affecting components of wing shape in Drosophila melanogaster. Genetics. 2000;155:671-83 pubmed
  9. Duchek P, Somogyi K, Jekely G, Beccari S, Rørth P. Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell. 2001;107:17-26 pubmed
    ..Intriguingly, the guidance function of PVR is largely redundant with that of EGFR. We present evidence implicating Rac and the Rac activator Mbc/DOCK180/CED-5 as mediators of the guidance signal. ..
  10. Schweitzer R, Shaharabany M, Seger R, Shilo B. Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. Genes Dev. 1995;9:1518-29 pubmed
    ..Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed...
  11. Macagno J, Díaz Vera J, Yu Y, MacPherson I, Sandilands E, Palmer R, et al. FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells. PLoS Genet. 2014;10:e1004262 pubmed publisher
    ..Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours. ..
  12. Dimitratos S, Woods D, Stathakis D, Bryant P. Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family. Bioessays. 1999;21:912-21 pubmed
    ..BioEssays 1999;21:912-921. ..
  13. Hayashi T, Kojima T, Saigo K. Specification of primary pigment cell and outer photoreceptor fates by BarH1 homeobox gene in the developing Drosophila eye. Dev Biol. 1998;200:131-45 pubmed
  14. Moressis A, Friedrich A, Pavlopoulos E, Davis R, Skoulakis E. A dual role for the adaptor protein DRK in Drosophila olfactory learning and memory. J Neurosci. 2009;29:2611-25 pubmed publisher
    ..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 ..
  15. Cooper J, Simon M, Kussick S. Signaling by ectopically expressed Drosophila Src64 requires the protein-tyrosine phosphatase corkscrew and the adapter downstream of receptor kinases. Cell Growth Differ. 1996;7:1435-41 pubmed
    ..We have investigated the roles that the adapter protein, Downstream of receptor kinases (Drk), and the SH2 domain-containing tyrosine phosphatase, Corkscrew (Csw), play in this process...
  16. Livingston B, Wilt F. Cell interactions in invertebrate development. Curr Opin Cell Biol. 1993;5:839-43 pubmed
  17. Oishi K, Zhang H, Gault W, Wang C, Tan C, Kim I, et al. Phosphatase-defective LEOPARD syndrome mutations in PTPN11 gene have gain-of-function effects during Drosophila development. Hum Mol Genet. 2009;18:193-201 pubmed publisher
  18. Yamamoto D. Signaling mechanisms in induction of the R7 photoreceptor in the developing Drosophila retina. Bioessays. 1994;16:237-44 pubmed
    ..It is plausible that the R7 precursor is actively prevented from taking on the neuronal fate and this inhibition is removed by activation of Sev. ..
  19. Zhang T, Branch A, Shen P. Octopamine-mediated circuit mechanism underlying controlled appetite for palatable food in Drosophila. Proc Natl Acad Sci U S A. 2013;110:15431-6 pubmed publisher
    ..Our findings provide fresh insight for the neurobiology and evolution of appetitive motivation. ..
  20. Tollinger M, Crowhurst K, Kay L, Forman Kay J. Site-specific contributions to the pH dependence of protein stability. Proc Natl Acad Sci U S A. 2003;100:4545-50 pubmed
    ..These interactions include a hydrogen bond between the Asp-8 side-chain and the Lys-21 backbone amide group in the folded state, which represents a highly conserved interaction in Src homology 3 domains. ..
  21. Vaizel Ohayon D, Schejter E. Mutations in centrosomin reveal requirements for centrosomal function during early Drosophila embryogenesis. Curr Biol. 1999;9:889-98 pubmed
    ..Centrosomin is an essential core component of early embryonic centrosomes in Drosophila. Microtubule-dependent events of early embryogenesis display differential requirements for centrosomal function. ..
  22. Cabernard C, Affolter M. Distinct roles for two receptor tyrosine kinases in epithelial branching morphogenesis in Drosophila. Dev Cell. 2005;9:831-42 pubmed
    ..Ras and the Mapk pathway are also needed for Egf-regulated cell division/survival, but Pointed is dispensable. ..
  23. Gilbert D. euGenes: a eukaryote genome information system. Nucleic Acids Res. 2002;30:145-8 pubmed
    ..These summarized data are useful for integration in other projects, such as gene expression databases. euGenes provides an extensible, flexible genome information system for many organisms. ..
  24. Wilson R, Leptin M. Fibroblast growth factor receptor-dependent morphogenesis of the Drosophila mesoderm. Philos Trans R Soc Lond B Biol Sci. 2000;355:891-5 pubmed
    ..Analysis of the function of dof, which encodes a cytoplasmic protein required for FGF signal transduction may provide an insight into these issues. ..
  25. Zhang O, Forman Kay J. Structural characterization of folded and unfolded states of an SH3 domain in equilibrium in aqueous buffer. Biochemistry. 1995;34:6784-94 pubmed
    ..form is similar to other known SH3 structures, especially the N-terminal SH3 domain of the mammalian homologue GRB2. A stretch of sequential amide-amide nuclear Overhauser effect cross-peaks for resonances of the unfolded state is ..
  26. Bergwitz C, Wee M, Sinha S, Huang J, Derobertis C, Mensah L, et al. Genetic determinants of phosphate response in Drosophila. PLoS ONE. 2013;8:e56753 pubmed publisher
    ..We identified a number of candidate genes potentially important for the cellular response to phosphate. Evaluation of 51 genes in live flies revealed some that affect larval development, adult life span and hemolymph phosphate levels. ..
  27. Lai K, Olivier J, Gish G, Henkemeyer M, McGlade J, Pawson T. A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase. Mol Cell Biol. 1995;15:4810-8 pubmed
    ..Despite the close relationship between the Drosophila and mammalian Shc proteins, dShc lacks the high-affinity Grb2-binding site found in mammalian Shc, suggesting that Shc proteins may have functions in addition to regulation of ..
  28. Li J, Li W. Drosophila gain-of-function mutant RTK torso triggers ectopic Dpp and STAT signaling. Genetics. 2003;164:247-58 pubmed
    ..These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism. ..
  29. Casci T, Vinós J, Freeman M. Sprouty, an intracellular inhibitor of Ras signaling. Cell. 1999;96:655-65 pubmed
    ..Sprouty binds to two intracellular components of the Ras pathway, Drk and Gap1. Our results indicate that Sprouty is a widespread inhibitor of Ras pathway signal transduction.
  30. Dawes Hoang R, Wieschaus E. Cell and developmental biology--a shared past, an intertwined future. Dev Cell. 2001;1:27-36 pubmed
    ..Our goal in this commentary is to examine the common origin of cell and developmental biology, to explore ways in which they currently interact, and to consider the connections and differences that exist between these two fields. ..
  31. Choy W, Mulder F, Crowhurst K, Muhandiram D, Millett I, Doniach S, et al. Distribution of molecular size within an unfolded state ensemble using small-angle X-ray scattering and pulse field gradient NMR techniques. J Mol Biol. 2002;316:101-12 pubmed
    The size distribution of molecules within an unfolded state of the N-terminal SH3 domain of drk (drkN SH3) has been studied by small-angle X-ray scattering (SAXS) and pulsed-field-gradient NMR (PFG-NMR) methods...
  32. Cleghon V, Feldmann P, Ghiglione C, Copeland T, Perrimon N, Hughes D, et al. Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway. Mol Cell. 1998;2:719-27 pubmed
    ..CSW also serves as an adaptor protein for DRK binding, physically linking Torso to Ras activation...
  33. Okabe M, Okano H. Two-step induction of chordotonal organ precursors in Drosophila embryogenesis. Development. 1997;124:1045-53 pubmed
    ..Three of these argos-expressing cells differentiate into the three remaining COPs and they prevent neighboring cells from becoming extra COPs. ..
  34. den Hertog J. Protein-tyrosine phosphatases in development. Mech Dev. 1999;85:3-14 pubmed
    ..Here I will introduce PTP-mediated signalling and discuss recent findings regarding the function of PTPs in development. ..
  35. Leevers S. What goes up must come down. Nat Cell Biol. 1999;1:E10-1 pubmed
  36. Fritz J, VanBerkum M. Calmodulin and son of sevenless dependent signaling pathways regulate midline crossing of axons in the Drosophila CNS. Development. 2000;127:1991-2000 pubmed
    ..These data suggest that Calmodulin and Son of sevenless signaling pathways function to interpret midline repulsive cues which prevent axons crossing the midline. ..
  37. Park J, Al Ramahi I, Tan Q, Mollema N, Diaz Garcia J, Gallego Flores T, et al. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013;498:325-331 pubmed publisher
    ..Collectively, these data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other classes of intractable neurodegenerative diseases. ..
  38. Tollinger M, Skrynnikov N, Mulder F, Forman Kay J, Kay L. Slow dynamics in folded and unfolded states of an SH3 domain. J Am Chem Soc. 2001;123:11341-52 pubmed
    15)N relaxation dispersion experiments were applied to the isolated N-terminal SH3 domain of the Drosophila protein drk (drkN SH3) to study microsecond to second time scale exchange processes...
  39. Tsarouhas V, Yao L, Samakovlis C. Src kinases and ERK activate distinct responses to Stitcher receptor tyrosine kinase signaling during wound healing in Drosophila. J Cell Sci. 2014;127:1829-39 pubmed publisher
    ..Here, we describe the immediate downstream effectors of Stit signaling in vivo. Drk (Downstream of receptor kinase) and Src family tyrosine kinases bind to the same docking site in the Stit intracellular domain...
  40. Kramer S, West S, Hiromi Y. Cell fate control in the Drosophila retina by the orphan receptor seven-up: its role in the decisions mediated by the ras signaling pathway. Development. 1995;121:1361-72 pubmed
    ..However, a decrease in ras signaling results in enhancement of the phenotype caused by the ro-svp transgene. We discuss the relationship between decisions controlled by seven-up and those controlled by ras signaling. ..
  41. Duffy J, Perrimon N. Recent advances in understanding signal transduction pathways in worms and flies. Curr Opin Cell Biol. 1996;8:231-8 pubmed
    ..Current work in both systems has provided new opportunities to investigate the potential for the cross-talk between these different signaling pathways. ..
  42. Klämbt C, Hummel T, Menne T, Sadlowski E, Scholz H, Stollewerk A. Development and function of embryonic central nervous system glial cells in Drosophila. Dev Genet. 1996;18:40-9 pubmed
    ..The longitudinal glia prefigure longitudinal axon paths and appear capable of regulating the expression of neuronal antigens. In the following we summarize the knowledge on the function of these glial cells. ..
  43. Li H, Chiang C, Huang H, Liaw G. mars and tousled-like kinase act in parallel to ensure chromosome fidelity in Drosophila. J Biomed Sci. 2009;16:51 pubmed publisher
  44. Bezsonova I, Singer A, Choy W, Tollinger M, Forman Kay J. Structural comparison of the unstable drkN SH3 domain and a stable mutant. Biochemistry. 2005;44:15550-60 pubmed
    The N-terminal SH3 domain of the Drosophila adapter protein Drk (drkN SH3 domain) is marginally stable (DeltaG(U) = 1 kcal/mol) and exists in equilibrium between folded and highly populated unfolded states...
  45. Pawson T, Olivier P, Rozakis Adcock M, McGlade J, Henkemeyer M. Proteins with SH2 and SH3 domains couple receptor tyrosine kinases to intracellular signalling pathways. Philos Trans R Soc Lond B Biol Sci. 1993;340:279-85 pubmed
    ..Evidence suggesting that SH2 and SH3 domains act synergistically in stimulation of the Ras pathway is discussed. ..
  46. Claeys I, Simonet G, Poels J, Van Loy T, Vercammen L, De Loof A, et al. Insulin-related peptides and their conserved signal transduction pathway. Peptides. 2002;23:807-16 pubmed
  47. Ishimaru S, Ueda R, Hinohara Y, Ohtani M, Hanafusa H. PVR plays a critical role via JNK activation in thorax closure during Drosophila metamorphosis. EMBO J. 2004;23:3984-94 pubmed
    ..In addition, we suppose that not only Rac but also Cdc42 is activated and involved in JNK activation downstream of PVR. ..
  48. Almudi I, Stocker H, Hafen E, Corominas M, Serras F. SOCS36E specifically interferes with Sevenless signaling during Drosophila eye development. Dev Biol. 2009;326:212-23 pubmed publisher
    ..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. ..
  49. Slack C, Alic N, Foley A, Cabecinha M, Hoddinott M, Partridge L. The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longevity. Cell. 2015;162:72-83 pubmed publisher
  50. Simon M, Dodson G, Rubin G. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. Cell. 1993;73:169-77 pubmed
    ..We have renamed the E(sev)2B locus downstream of receptor kinases (drk).
  51. Hafen E, Dickson B, Brunner T, Raabe T. Genetic dissection of signal transduction mediated by the sevenless receptor tyrosine kinase in Drosophila. Philos Trans R Soc Lond B Biol Sci. 1993;340:273-8 pubmed
    ..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. ..
  52. Simon M, Bowtell D, Dodson G, Laverty T, Rubin G. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Cell. 1991;67:701-16 pubmed
    ..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. ..
  53. Gregory S, Brown N. kakapo, a gene required for adhesion between and within cell layers in Drosophila, encodes a large cytoskeletal linker protein related to plectin and dystrophin. J Cell Biol. 1998;143:1271-82 pubmed
    ..Kakapo is also expressed more widely at a lower level where it is essential for epidermal cell layer stability. These results suggest that the Kakapo protein forms essential links among integrins, actin, and microtubules. ..
  54. Raabe T, Olivier J, Dickson B, Liu X, Gish G, Pawson T, et al. Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila. EMBO J. 1995;14:2509-18 pubmed
    The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila...
  55. Charng W, Yamamoto S, Bellen H. Shared mechanisms between Drosophila peripheral nervous system development and human neurodegenerative diseases. Curr Opin Neurobiol. 2014;27:158-64 pubmed publisher
    ..In this review, we summarize and discuss how studies of Drosophila PNS and NMJ development have provided guidance in experimental approaches for these diseases. ..
  56. Rice D, Curran T. Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS. Genes Dev. 1999;13:2758-73 pubmed
  57. Ishimaru S, Williams R, Clark E, Hanafusa H, Gaul U. Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1. EMBO J. 1999;18:145-55 pubmed
    ..report the identification of Drosophila C3G, which, like its human cognate, specifically binds to CRK but not DRK/GRB2 adaptor molecules...
  58. Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003;13:79-85 pubmed
    ..This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth. ..
  59. Simon M. Signal transduction during the development of the Drosophila R7 photoreceptor. Dev Biol. 1994;166:431-42 pubmed
  60. Choy W, Forman Kay J. Calculation of ensembles of structures representing the unfolded state of an SH3 domain. J Mol Biol. 2001;308:1011-32 pubmed
    The N-terminal SH3 domain of drk (drkN SH3 domain) exists in equilibrium between a folded (F(exch)) and an unfolded (U(exch)) form under non-denaturing conditions...
  61. Kim S, Kim J, Malik S, Son W, Kwon K, Kim C. Negative regulation of EGFR/MAPK pathway by Pumilio in Drosophila melanogaster. PLoS ONE. 2012;7:e34016 pubmed publisher
    ..Taken together, our evidence suggests that Pum functions as a negative regulator of EGFR signaling by directly targeting components of the pathway in Drosophila. ..
  62. Yan H, Chin M, Horvath E, Kane E, Pfleger C. Impairment of ubiquitylation by mutation in Drosophila E1 promotes both cell-autonomous and non-cell-autonomous Ras-ERK activation in vivo. J Cell Sci. 2009;122:1461-70 pubmed publisher
    ..E1 hypomorphs is dramatically suppressed by removing one copy of Ras, removal of the more upstream components Egfr, Grb2 or sos shows no suppression...
  63. Kundrotas P, Karshikoff A. Charge sequence coding in statistical modeling of unfolded proteins. Biochim Biophys Acta. 2004;1702:1-8 pubmed
    ..This was illustrated by comparison of the pK values of the titratable groups of the unfolded N-terminal SH3 domain of the Drosophila protein drk to the available experimental data.
  64. Settle M, Gordon M, Nadella M, Dankort D, Muller W, Jacobs J. Genetic identification of effectors downstream of Neu (ErbB-2) autophosphorylation sites in a Drosophila model. Oncogene. 2003;22:1916-26 pubmed
    ..Signalling from pTyr (YB) was affected by a haplosufficiency in drk (Grb-2), and in genes thought to function downstream of Grb-2: dab, sos, csw (Shp-2), and dos (Gab-1)...
  65. Hafen E, Dickson B, Raabe T, Brunner D, Oellers N, van der Straten A. Genetic analysis of the sevenless signal transduction pathway of Drosophila. Dev Suppl. 1993;:41-6 pubmed
    ..In contrast to the receptor and its ligand, these components are shared between different signal transduction pathways not only in Drosophila but homologous components are also involved in signal transduction in other organisms. ..
  66. Kosmidis S, Grammenoudi S, Papanikolopoulou K, Skoulakis E. Differential effects of Tau on the integrity and function of neurons essential for learning in Drosophila. J Neurosci. 2010;30:464-77 pubmed publisher
    ..The data support the notion that phosphorylation at particular sites rather than hyperphosphorylation per se mediates toxicity or dysfunction in a cell type-specific manner. ..
  67. Wang P, Pai L. D-Cbl binding to Drk leads to dose-dependent down-regulation of EGFR signaling and increases receptor-ligand endocytosis. PLoS ONE. 2011;6:e17097 pubmed publisher
    ..Here, we determined the underlying molecular mechanism, and found that Drk facilitates the dose-dependent regulation of EGFR signaling through binding to the proline-rich motif of D-CblL, PR...
  68. Pawson T. Signal transduction--a conserved pathway from the membrane to the nucleus. Dev Genet. 1993;14:333-8 pubmed
  69. Dickson B. Nuclear factors in sevenless signalling. Trends Genet. 1995;11:106-11 pubmed
  70. Woodcock S, Hughes D. p120 Ras GTPase-activating protein associates with fibroblast growth factor receptors in Drosophila. Biochem J. 2004;380:767-74 pubmed
    ..On the basis of these results, we propose that RasGAP is directly recruited into activated FGFRs in Drosophila and plays a role in regulating the strength of signalling through Ras and the mitogen-activated protein kinase pathway. ..
  71. Le N, Simon M. Disabled is a putative adaptor protein that functions during signaling by the sevenless receptor tyrosine kinase. Mol Cell Biol. 1998;18:4844-54 pubmed
    DRK, the Drosophila homolog of the SH2-SH3 domain adaptor protein Grb2, is required during signaling by the sevenless receptor tyrosine kinase (SEV). One role of DRK is to provide a link between activated SEV and the Ras1 activator SOS...
  72. Doyle H, Bishop J. Torso, a receptor tyrosine kinase required for embryonic pattern formation, shares substrates with the sevenless and EGF-R pathways in Drosophila. Genes Dev. 1993;7:633-46 pubmed
    ..The phenotypes of several other Su(tor) mutations suggest that they also function in other receptor tyrosine kinase-activated pathways at different times during Drosophila development. ..
  73. Innocenti P, Chenoweth S. Interspecific divergence of transcription networks along lines of genetic variance in Drosophila: dimensionality, evolvability, and constraint. Mol Biol Evol. 2013;30:1358-67 pubmed publisher
  74. Boedigheimer M, Bryant P, Laughon A. Expanded, a negative regulator of cell proliferation in Drosophila, shows homology to the NF2 tumor suppressor. Mech Dev. 1993;44:83-4 pubmed
  75. MacDougall L, Gagou M, Leevers S, Hafen E, Waterfield M. Targeted expression of the class II phosphoinositide 3-kinase in Drosophila melanogaster reveals lipid kinase-dependent effects on patterning and interactions with receptor signaling pathways. Mol Cell Biol. 2004;24:796-808 pubmed
    ..A class II polyproline motif in PI3K_68D can bind the Drk adaptor protein in vitro, primarily via the N-terminal SH3 domain of Drk...
  76. Crowhurst K, Tollinger M, Forman Kay J. Cooperative interactions and a non-native buried Trp in the unfolded state of an SH3 domain. J Mol Biol. 2002;322:163-78 pubmed
    The presence of residual structure in the unfolded state of the N-terminal SH3 domain of Drosophila drk (drkN SH3 domain) has been investigated using far- and near-UV circular dichroism (CD), fluorescence, and NMR spectroscopy...
  77. Tutor A, Prieto Sánchez S, Ruiz Gomez M. Src64B phosphorylates Dumbfounded and regulates slit diaphragm dynamics: Drosophila as a model to study nephropathies. Development. 2014;141:367-76 pubmed publisher
  78. Ahern Djamali S, Bachmann C, Hua P, Reddy S, Kastenmeier A, Walter U, et al. Identification of profilin and src homology 3 domains as binding partners for Drosophila enabled. Proc Natl Acad Sci U S A. 1999;96:4977-82 pubmed
    ..These data support the hypothesis that Ena provides a regulated link between signal transduction and cytoskeleton assembly in the developing Drosophila embryo. ..
  79. Lu T, Doherty J, Freeman M. DRK/DOS/SOS converge with Crk/Mbc/dCed-12 to activate Rac1 during glial engulfment of axonal debris. Proc Natl Acad Sci U S A. 2014;111:12544-9 pubmed publisher
    ..Here we show that the signaling molecules downstream of receptor kinase (DRK) and daughter of sevenless (DOS) (mammalian homologs, Grb2 and Gab2, respectively) and the GEF ..