src genes

Summary

Summary: Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20.

Top Publications

  1. Jähner D, Hunter T. The stimulation of quiescent rat fibroblasts by v-src and v-fps oncogenic protein-tyrosine kinases leads to the induction of a subset of immediate early genes. Oncogene. 1991;6:1259-68 pubmed
    ..Furthermore, we demonstrated that the induction of several of these genes by the retroviral oncogenic protein-tyrosine kinases is rapid, direct and occurs at the transcriptional level. ..
  2. Irby R, Mao W, Coppola D, Kang J, Loubeau J, Trudeau W, et al. Activating SRC mutation in a subset of advanced human colon cancers. Nat Genet. 1999;21:187-90 pubmed
    ..These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer. ..
  3. Dunlap D, Ikeda I, Nagashima H, Vogel C, Matsumura F. Effects of src-deficiency on the expression of in vivo toxicity of TCDD in a strain of c-src knockout mice procured through six generations of backcrossings to C57BL/6 mice. Toxicology. 2002;172:125-41 pubmed
    ..These findings suggest that the absence of c-src expression indeed affects the development of selected, TCDD-induced toxic endpoints that are related to wasting syndrome. ..
  4. Malek R, Irby R, Guo Q, Lee K, Wong S, He M, et al. Identification of Src transformation fingerprint in human colon cancer. Oncogene. 2002;21:7256-65 pubmed
    ..Supportive Supplemental Data can be viewed at http://pga.tigr.org/PGApubs.shtml. ..
  5. Schuuring E, Verhoeven E, Litvinov S, Michalides R. The product of the EMS1 gene, amplified and overexpressed in human carcinomas, is homologous to a v-src substrate and is located in cell-substratum contact sites. Mol Cell Biol. 1993;13:2891-98 pubmed
  6. Liu Y, Gao L, Gelman I. SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis. BMC Cancer. 2006;6:105 pubmed
    ..Our data provide further evidence that SSeCKS can suppress Src-induced oncogenesis by modulating gene expression downstream of Src kinase activity. ..
  7. Kubota Y, Tanaka T, Kitanaka A, Ohnishi H, Okutani Y, Waki M, et al. Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase. EMBO J. 2001;20:5666-77 pubmed
    ..Taken together, Src transduces the erythropoietin-induced erythroid differentiation signals by regulating PI3-kinase activity. ..
  8. Gagliardi M, Maynard S, Bojovic B, Bedard P. The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPbeta in v-src transformed chicken embryo fibroblasts. Oncogene. 2001;20:2301-13 pubmed
    ..Therefore, the activation of C/EBPbeta is important for the expression of v-src regulated genes but is not required for the in vitro transformation of CEF by pp60(v-src). ..
  9. Masker K, Golden A, Gaffney C, Mazack V, Schwindinger W, Zhang W, et al. Transcriptional profile of Rous Sarcoma Virus transformed chicken embryo fibroblasts reveals new signaling targets of viral-src. Virology. 2007;364:10-20 pubmed
    ..The set of strongly repressed genes contains TGF beta 3, TGF beta-induced gene, and deiodinase. The function of several robustly modulated genes sheds new light on the molecular mechanism of oncogenic transformation. ..

More Information

Publications62

  1. Moissoglu K, Gelman I. v-Src rescues actin-based cytoskeletal architecture and cell motility and induces enhanced anchorage independence during oncogenic transformation of focal adhesion kinase-null fibroblasts. J Biol Chem. 2003;278:47946-59 pubmed
    ..Overall, our data indicate that FAK, although dispensable, attenuates v-Src-induced oncogenic transformation by modulating distinct signaling and cytoskeletal pathways. ..
  2. Lin X, Nelson P, Frankfort B, Tombler E, Johnson R, Gelman I. Isolation and characterization of a novel mitogenic regulatory gene, 322, which is transcriptionally suppressed in cells transformed by src and ras. Mol Cell Biol. 1995;15:2754-62 pubmed
    ..Thus, 322 represent a novel src- and ras-regulated gene which encodes a potential regulator of mitogenesis and/or tumor suppressor. ..
  3. Feng G, Hui C, Pawson T. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases. Science. 1993;259:1607-11 pubmed
    ..The Syp gene is widely expressed throughout embryonic mouse development and in adult tissues. Thus, Syp may function in mammalian embryonic development and as a common target of both receptor and nonreceptor tyrosine kinases. ..
  4. Lau A. c-Src: bridging the gap between phosphorylation- and acidification-induced gap junction channel closure. Sci STKE. 2005;2005:pe33 pubmed
  5. Klages S, Adam D, Eiseman E, Fargnoli J, Dymecki S, Desiderio S, et al. Molecular cloning and analysis of cDNA encoding the murine c-yes tyrosine protein kinase. Oncogene. 1993;8:713-9 pubmed
    ..The reading frame encodes a protein of 541 amino acids with a calculated molecular mass of 60.63 kDa that is reactive with anti-Yes antisera and possesses protein kinase activity. ..
  6. Debruyne P, Bruyneel E, Karaguni I, Li X, Flatau G, Muller O, et al. Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways. Oncogene. 2002;21:6740-50 pubmed
    ..We conclude that bile acids stimulate invasion and haptotaxis in colorectal cancer cells via several cancer invasion signaling pathways. ..
  7. Diaz B, Barnard D, Filson A, Macdonald S, King A, Marshall M. Phosphorylation of Raf-1 serine 338-serine 339 is an essential regulatory event for Ras-dependent activation and biological signaling. Mol Cell Biol. 1997;17:4509-16 pubmed
  8. Stetak A, Csermely P, Ullrich A, Keri G. Physical and functional interactions between protein tyrosine phosphatase alpha, PI 3-kinase, and PKCdelta. Biochem Biophys Res Commun. 2001;288:564-72 pubmed
    ..Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232. ..
  9. Plachý J, Hejnar J, Trtkova K, Trejbalova K, Svoboda J, Hala K. DNA vaccination against v-src oncogene-induced tumours in congenic chickens. Vaccine. 2001;19:4526-35 pubmed
    ..In the CC line chickens we observed tumour growth retardation after a low-dose DNA vaccination administered to immature recipients while higher amounts of DNA vaccine in immunocompetent chickens exerted an enhancing effect...
  10. Hisano C, Tanaka R, Fujishima H, Ariyama H, Tsuchiya T, Tatsumoto T, et al. Suppression of anoikis by v-Src but not by activated c-H-ras in human gallbladder epithelial cells. Cell Biol Int. 2003;27:415-21 pubmed
    ..These data suggest that the ability of activated Src to prevent anoikis may be mediated by Src to a downstream signaling pathway involving FAK, but not Ras, PI-3 kinase, or PKC. ..
  11. Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, et al. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993;361:226-33 pubmed
    ..The gene is a member of the src family of proto-oncogenes which encode protein-tyrosine kinases. This is, to our knowledge, the first evidence that mutations in a src-related gene are involved in human genetic disease. ..
  12. Baba O, Miyata A, Abe T, Shibata S, Nakano Y, Terashima T, et al. Formation of acellular cementum-like layers, with and without extrinsic fiber insertion, along inert bone surfaces of aging c-Src gene knockout mice. Eur J Oral Sci. 2006;114:524-34 pubmed
  13. Sargiacomo M, Scherer P, Tang Z, Casanova J, Lisanti M. In vitro phosphorylation of caveolin-rich membrane domains: identification of an associated serine kinase activity as a casein kinase II-like enzyme. Oncogene. 1994;9:2589-95 pubmed
  14. Kotani T, Morone N, Yuasa S, Nada S, Okada M. Constitutive activation of neuronal Src causes aberrant dendritic morphogenesis in mouse cerebellar Purkinje cells. Neurosci Res. 2007;57:210-9 pubmed
    ..These results suggest that n-Src activity regulates the dendritic morphogenesis of Purkinje cells through affecting microtubule organization. ..
  15. Fabarius A, Giehl M, Rebacz B, Krämer A, Frank O, Haferlach C, et al. Centrosome aberrations and G1 phase arrest after in vitro and in vivo treatment with the SRC/ABL inhibitor dasatinib. Haematologica. 2008;93:1145-54 pubmed publisher
    ..Dasatinib blocks the G(1)/S transition and inhibits cell growth. It induces centrosomal aberrations and a decrease of mitotic spindles. The effects suggest an involvement of SRC and ABL inhibition. ..
  16. Schaffhausen B, Roberts T. Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer. Virology. 2009;384:304-16 pubmed publisher
    ..There remain many opportunities as we seek a full molecular understanding of MT and apply some of its lessons to human cancer...
  17. Umemoto T, Inomoto T, Ueda K, Hamaguchi M, Kioka N. v-Src-mediated transformation suppresses the expression of focal adhesion protein vinexin. Cancer Lett. 2009;279:22-9 pubmed publisher
    ..Taken together, these observations suggest that cellular transformation by v-Src suppressed vinexin expression and that down-regulation of vinexin may be associated with oncogenic transformation. ..
  18. Harris D, Bonfil D, Chuderland D, Kraus S, Seger R, Naor Z. Activation of MAPK cascades by GnRH: ERK and Jun N-terminal kinase are involved in basal and GnRH-stimulated activity of the glycoprotein hormone LHbeta-subunit promoter. Endocrinology. 2002;143:1018-25 pubmed
    ..We conclude that ERK and JNK are involved in basal and GnRH-A stimulation of LHbeta-CAT activity. c-Src participates also in LHbeta-promoter activation by a mechanism which might be linked to ERK and JNK activation. ..
  19. Gala M, Sun R, Yang V. Inhibition of cell transformation by sulindac sulfide is confined to specific oncogenic pathways. Cancer Lett. 2002;175:89-94 pubmed
    ..Further studies of the sulindac-resistant oncogenic pathways may lead to identification of novel therapeutic agents that are effective in the prevention or treatment of CRC. ..
  20. Marx M, Warren S, Madri J. pp60(c-src) modulates microvascular endothelial phenotype and in vitro angiogenesis. Exp Mol Pathol. 2001;70:201-13 pubmed
  21. Zhen X, Zhang J, Johnson G, Friedman E. D(4) dopamine receptor differentially regulates Akt/nuclear factor-kappa b and extracellular signal-regulated kinase pathways in D(4)MN9D cells. Mol Pharmacol. 2001;60:857-64 pubmed
    ..We also demonstrated that D(4) receptor-stimulated cell proliferation is mediated by the Src/SHC/Ras/ERK pathway. ..
  22. Chou M, Hanafusa H. A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain. J Biol Chem. 1995;270:7359-64 pubmed
    ..NAK is complexed with Nck in a wide variety of cell types, including NIH3T3, A431, PC12, and Hela cells. ..
  23. Dutartre H, Harris M, Olive D, Collette Y. The human immunodeficiency virus type 1 Nef protein binds the Src-related tyrosine kinase Lck SH2 domain through a novel phosphotyrosine independent mechanism. Virology. 1998;247:200-11 pubmed
    ..Together, our results establish different mechanisms for Hck and Lck binding by HIV-1 Nef protein, and identify a novel mechanism for Src-like tyrosine kinase targeting by a viral protein. ..
  24. Ishizawar R, Parsons S. c-Src and cooperating partners in human cancer. Cancer Cell. 2004;6:209-14 pubmed
    ..Because of its important role in these oncogenic processes, it represents a therapeutic target ripe for exploitation. ..
  25. Brabek J, Constancio S, Shin N, Pozzi A, Weaver A, Hanks S. CAS promotes invasiveness of Src-transformed cells. Oncogene. 2004;23:7406-15 pubmed
    ..Thus, elevated CAS-associated tyrosine phosphorylation signaling events occurring at sites of integrin-mediated cell adhesion can have a major role in the development of an invasive cell phenotype. ..
  26. Payne G, Shoelson S, Gish G, Pawson T, Walsh C. Kinetics of p56lck and p60src Src homology 2 domain binding to tyrosine-phosphorylated peptides determined by a competition assay or surface plasmon resonance. Proc Natl Acad Sci U S A. 1993;90:4902-6 pubmed
    ..Lowest affinity (80- to 300-fold lower) was observed with phosphopeptides corresponding to phosphorylated tyrosines of GTPase-activating protein, insulin receptor substrate 1, and SH2 domain-containing protein-tyrosine-phosphatase 1. ..
  27. Barboza J, Wang S, Schaefer T. Generation and characterization of a constitutively active Stat3 protein. Mol Biol Rep. 2004;31:13-21 pubmed
  28. Bonham K, Fujita D. Organization and analysis of the promoter region and 5' non-coding exons of the human c-src proto-oncogene. Oncogene. 1993;8:1973-81 pubmed
    ..S1 analyses of human c-src mRNA from cell lines indicated that multiple transcription start sites were utilized. ..
  29. Villa Moruzzi E, Puntoni F. Phosphorylation of phosphatase-1alpha in cells expressing v-src. Biochem Biophys Res Commun. 1996;219:863-7 pubmed
    ..Assay of the three immunoprecipitated PP1 isoforms indicated that only PP1alpha was inactivated. Altogether the data suggest that PP1alpha might be a target of v-src "in vivo". ..
  30. Buckhaults P, Chen L, Fregien N, Pierce M. Transcriptional regulation of N-acetylglucosaminyltransferase V by the src oncogene. J Biol Chem. 1997;272:19575-81 pubmed
    ..src stimulation of transcription from this region was inhibited by co-transfection with a dominant-negative mutant of Ets-2, demonstrating that the effects of the src kinase on GlcNAc-T V expression are dependent on Ets. ..
  31. Zou L, Wang Z, Shen L, Bao G, Wang T, Kang J, et al. Receptor tyrosine kinases positively regulate BACE activity and Amyloid-beta production through enhancing BACE internalization. Cell Res. 2007;17:389-401 pubmed
  32. Brabek J, Mojzita D, Hamplová L, Folk P. The regulatory region of Prague C v-Src inhibits the activity of the Schmidt-Ruppin A v-Src kinase domain. Folia Biol (Praha). 2002;48:28-33 pubmed
  33. Miki H, Miura K, Matuoka K, Nakata T, Hirokawa N, Orita S, et al. Association of Ash/Grb-2 with dynamin through the Src homology 3 domain. J Biol Chem. 1994;269:5489-92 pubmed
    ..These data show that Ash SH3 domains bind to the proline-rich region of dynamin. Considering the function of dynamin in membrane trafficking, Ash may regulate endocytosis in addition to Ras activation. ..
  34. Brabek J, Mojzita D, Puta F. Expression of protein tyrosine kinase pp60v-src variants in Dictyostelium discoideum. Folia Biol (Praha). 2002;48:73-6 pubmed
    ..In contrast to other lower eukaryotes, where the accumulation of v-Src leads to growth inhibition, D. discoideum cells silenced the kinase activity of PRC-derived v-Src and showed no developmental or growth defects. ..
  35. Crenshaw E, Ryan A, Dillon S, Kalla K, Rosenfeld M. Wocko, a neurological mutant generated in a transgenic mouse pedigree. J Neurosci. 1991;11:1524-30 pubmed
  36. Weng Z, Thomas S, Rickles R, Taylor J, Brauer A, Seidel Dugan C, et al. Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains. Mol Cell Biol. 1994;14:4509-21 pubmed
  37. Maerkel K, Durrer S, Henseler M, Schlumpf M, Lichtensteiger W. Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: developmental exposure of rats to 4-methylbenzylidene camphor. Toxicol Appl Pharmacol. 2007;218:152-65 pubmed
    ..The data indicate profound sex- and region-specific alterations in the regulation of estrogen target genes at brain level. Effect patterns in baseline and E2-induced gene expression differ from those in uterus and prostate. ..
  38. Zhuang S, Schnellmann R. Suramin promotes proliferation and scattering of renal epithelial cells. J Pharmacol Exp Ther. 2005;314:383-90 pubmed
    ..Furthermore, suramin-induced outgrowth, scattering, and proliferation of RPTC are through Src-mediated activation of the PI3K pathway but not ERK1/2 or the EGF receptor. ..
  39. Irby R, Malek R, Bloom G, Tsai J, Letwin N, Frank B, et al. Iterative microarray and RNA interference-based interrogation of the SRC-induced invasive phenotype. Cancer Res. 2005;65:1814-21 pubmed
    ..In this manner, numerous members of a "transcriptional cascade" pathway for metastatic activity have been identified and functionally validated. ..
  40. Frame M. Newest findings on the oldest oncogene; how activated src does it. J Cell Sci. 2004;117:989-98 pubmed
    ..A recurring theme is the identification of novel and important Src substrates that mediate key biological events associated with transformation. ..
  41. Fuller S, Gillespie Brown J, Sugden P. Oncogenic src, raf, and ras stimulate a hypertrophic pattern of gene expression and increase cell size in neonatal rat ventricular myocytes. J Biol Chem. 1998;273:18146-52 pubmed
    ..We conclude that members of the Src family of tyrosine kinases may be important in mediating the transcriptional changes occurring during cardiac myocyte hypertrophy and that Ras and Raf may be downstream effectors. ..
  42. Hoelper P, Faust D, Oesch F, Dietrich C. Evaluation of the role of c-Src and ERK in TCDD-dependent release from contact-inhibition in WB-F344 cells. Arch Toxicol. 2005;79:201-7 pubmed
    ..Our data show that neither c-Src-activation, nor ERK-activation are required for TCDD-dependent release from contact-inhibition arguing against a functional role of EGF-receptor activation in response to TCDD in WB-F344 cells. ..
  43. Duffy H, Delmar M, Coombs W, Tafftet S, Hertzberg E, Spray D. Functional demonstration of connexin-protein binding using surface plasmon resonance. Cell Commun Adhes. 2001;8:225-9 pubmed
    ..The combined application of proteomic and functional studies is expected to identify which proteins within heart tissue interact with Cx43 and what roles they may play in gap junction function. ..
  44. Feuer G, Lee W, Pattengale P, Fan H. Specificity of disease induced by M-MuLV chimeric retroviruses containing v-myc or v-src is not determined by the LTR. Virology. 1993;195:286-91 pubmed
    ..However, substitution of the LTRs did affect the efficiency of tumorigenesis. ..
  45. Iacovelli L, Capobianco L, Iula M, Di Giorgi Gerevini V, Picascia A, Blahos J, et al. Regulation of mGlu4 metabotropic glutamate receptor signaling by type-2 G-protein coupled receptor kinase (GRK2). Mol Pharmacol. 2004;65:1103-10 pubmed
    ..We speculate that GRK2 acts as a "switch molecule" by inhibiting the mGlu4 receptor-mediated stimulation of MAPK and therefore directing the signal propagation toward the inhibition of adenylyl cyclase. ..
  46. Yeo M, Partridge M, Ezratty E, Shen Q, Gundersen G, Marcantonio E. Src SH2 arginine 175 is required for cell motility: specific focal adhesion kinase targeting and focal adhesion assembly function. Mol Cell Biol. 2006;26:4399-409 pubmed
  47. Sideras P, Muller S, Shiels H, Jin H, Khan W, Nilsson L, et al. Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci. J Immunol. 1994;153:5607-17 pubmed
    ..The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule. ..
  48. Bache K, Raiborg C, Mehlum A, Madshus I, Stenmark H. Phosphorylation of Hrs downstream of the epidermal growth factor receptor. Eur J Biochem. 2002;269:3881-7 pubmed
    ..These results suggest that Hrs is a substrate for several kinases downstream of the EGF receptor. ..
  49. Hynes N. Tyrosine kinase signalling in breast cancer. Breast Cancer Res. 2000;2:154-7 pubmed
    ..This topic is the major focus of the thematic review section of this issue of Breast Cancer Research. ..
  50. Jiao X, Katiyar S, Liu M, Mueller S, Lisanti M, Li A, et al. Disruption of c-Jun reduces cellular migration and invasion through inhibition of c-Src and hyperactivation of ROCK II kinase. Mol Biol Cell. 2008;19:1378-90 pubmed publisher
    ..As c-Src is a critical component of pathways regulating proliferation, survival, and metastasis, the induction of c-Src abundance, by c-Jun, provides a novel mechanism of cooperative signaling in cellular invasion. ..
  51. Windham T, Parikh N, Siwak D, Summy J, McConkey D, Kraker A, et al. Src activation regulates anoikis in human colon tumor cell lines. Oncogene. 2002;21:7797-807 pubmed
    ..These results suggest that Src activation may contribute to colon tumor progression and metastasis in part by activating Akt-mediated survival pathways that decrease sensitivity of detached cells to anoikis. ..
  52. Jiang K, Delarue F, Sebti S. EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation. Oncogene. 2004;23:1136-45 pubmed
    ..Taken together the data suggest that certain oncogenes suppress RhoB as one of the critical steps leading to malignant transformation. ..
  53. Songyang Z, Shoelson S, McGlade J, Olivier P, Pawson T, Bustelo X, et al. Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol. 1994;14:2777-85 pubmed
    ..SHC is predicted to bind to a subgroup og these same motifs. A structural basis for the association of Csk with Src family members is also suggested from these studies. ..