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Gene Review

Fyn  -  Fyn proto-oncogene

Mus musculus

Synonyms: AI448320, AW552119, Proto-oncogene c-Fyn, Src Kinase p59, Tyrosine-protein kinase Fyn, ...
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Disease relevance of Fyn


Psychiatry related information on Fyn


High impact information on Fyn

  • Upon integrin ligation, Fyn is activated and binds, via its SH3 domain, to Shc [11].
  • A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth [11].
  • Cells derived from these embryos exhibit an order of magnitude increase in activity of Src and the related Fyn kinase [12].
  • VEGF induction by hypoxia in c-src(-) cells is impaired, although there is a compensatory activation of Fyn [13].
  • Crosslinking of large MAG with antibody induces a rapid increase in the specific activity of Fyn kinase [14].

Chemical compound and disease context of Fyn


Biological context of Fyn


Anatomical context of Fyn

  • Here we show that the combined disruption of Lck and Fyn (lck(-/-)fyn(-/-)) completely arrests alpha beta T cell development at the CD4-CD8- stage [22].
  • Fyn is localized in the cortex region underneath the plasma membrane in mouse oocytes [19].
  • Finally, microinjection of constitutively active Fyn triggers oocyte activation downstream of tr-kit but still requires PLC activity [19].
  • NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice [23].
  • Haploinsufficiency or complete deficiency of protein kinase C beta, Fyn, CD22, Galphaq, or Galpha11 had no detectable effect on the function of Btk(lo) B cells [24].

Associations of Fyn with chemical compounds

  • Initial events of myelination involve Fyn tyrosine kinase signalling [14].
  • In this study, we examined how Fyn participates in synaptic plasticity by analyzing the physical and functional interaction between Fyn and NMDA receptors [25].
  • Unlike the current prevailing model, Fyn-induced activation of Ras might involve the stimulation of the catalytic guanine nucleotide exchange activity of mSOS [20].
  • Fyn-mediated tyrosine phosphorylation of N-methyl-D-aspartate (NMDA) receptor subunits has been implicated in various brain functions, including ethanol tolerance, learning, and seizure susceptibility [1].
  • These data suggest the unexpected conclusion that the Fyn SH2 domain may bind to Cbl in a phosphotyrosine-independent manner [26].
  • Together, these data demonstrate crosstalk between Src-family kinase activity and fatty acid oxidation and show that the loss of Fyn markedly improves peripheral tissue insulin sensitivity by relieving a selective negative modulation of AMP kinase activity in adipose tissue and skeletal muscle [27].

Physical interactions of Fyn

  • The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation [28].
  • Kv2.1- channel subunits are found to interact with the Fyn SH2 domain [29].
  • We suggest that AChRs are initially phosphorylated by Src and subsequently bind Fyn in a phosphotyrosine-dependent manner [30].
  • We utilized yeast two-hybrid cloning to identify the product of the tctex-1 gene as a protein that specifically interacts with Fyn, but not with other Src family kinases [31].
  • We also present the isolation and in vitro characterization of Fyn SH3-derived proteins binding to the extra-domain B of fibronectin, a marker of angiogenesis [32].

Enzymatic interactions of Fyn

  • The Fyn SH2 domain bound to both tyrosine-phosphorylated and nonphosphorylated Cbl, implying that this interaction might be phosphotyrosine-independent [33].
  • Recombinant PSD-93 was phosphorylated by Fyn in vitro, and Tyr-384 was identified as a major phosphorylation site [34].
  • When fyn copy number is reduced, src, but not yes, becomes important, reflecting a partial redundancy between fyn and src.CONCLUSIONS: Reelin activates Fyn to phosphorylate and downregulate Dab1 during brain development [35].
  • Thus, we propose that Fyn phosphorylates and activates ZAP-70 and that both kinases cooperate in TCR signaling [36].
  • Seven out of 25 tyrosine residues in the C-terminal cytoplasmic region of GluR epsilon 2 were phosphorylated by Fyn in vitro [37].

Co-localisations of Fyn


Regulatory relationships of Fyn

  • Protein tyrosine phosphatase alpha regulates Fyn activity and Cbp/PAG phosphorylation in thymocyte lipid rafts [40].
  • The epitope-tagged Efs was hyperphosphorylated when cotransfected with a vector expressing Fyn [41].
  • Thus, the NMDA-R protein level is regulated by the Reelin protein level in a Fyn-dependent manner in the mouse brain [42].
  • Overexpression of Fyn mutants with an activated kinase mutation and with a Src homology 2 deletion mutation resulted in a stimulation and suppression of the mSOS activity, respectively [20].
  • Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells [20].

Other interactions of Fyn

  • These observations reveal that Fyn can subserve some Lck-like functions in T cell development [43].
  • However the Itk/Fyn doubly deficient mice exhibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone [18].
  • We show that the Src-like kinase Fyn phosphorylates Tyr161 in tr-kit and that this residue is essential for tr-kit function [19].
  • We infer from these results that both Fyn and Lyn are required and that their signals are synergistic for B cell triggering after CD38 ligation [44].
  • The deficiency in Vav phosphorylation in Fyn-deficient T cells was associated with a defect in the formation of APC-T cell conjugates when T cells were stimulated with either agonist or antagonist peptide [45].

Analytical, diagnostic and therapeutic context of Fyn


  1. Fyn is required for haloperidol-induced catalepsy in mice. Hattori, K., Uchino, S., Isosaka, T., Maekawa, M., Iyo, M., Sato, T., Kohsaka, S., Yagi, T., Yuasa, S. J. Biol. Chem. (2006) [Pubmed]
  2. Muscarinic M2 receptors mediate transactivation of EGF receptor through Fyn kinase and without matrix metalloproteases. Stirnweiss, J., Valkova, C., Ziesché, E., Drube, S., Liebmann, C. Cell. Signal. (2006) [Pubmed]
  3. EGF-R signaling through Fyn kinase disrupts the function of integrin alpha6beta4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion. Mariotti, A., Kedeshian, P.A., Dans, M., Curatola, A.M., Gagnoux-Palacios, L., Giancotti, F.G. J. Cell Biol. (2001) [Pubmed]
  4. The proliferative in vivo activities of lpr double-negative T cells and the primary role of p59fyn in their activation and expansion. Balomenos, D., Rumold, R., Theofilopoulos, A.N. J. Immunol. (1997) [Pubmed]
  5. Induction of interleukin-2 transcription by the hamster polyomavirus middle T antigen: a role for Fyn in T cell signal transduction. Brizuela, L., Ulug, E.T., Jones, M.A., Courtneidge, S.A. Eur. J. Immunol. (1995) [Pubmed]
  6. Decreased locomotor activity in mice carrying transgenic Fyn tyrosine kinase. Ishibashi, H., Kojima, N., Obata, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  7. Resistance to alcohol withdrawal-induced behaviour in Fyn transgenic mice and its reversal by ifenprodil. Stork, O., Kojima, N., Stork, S., Kume, N., Obata, K. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  8. Exposure to hexanal odor influences maternal behavior and induces neonatal death in Fyn tyrosine kinase-deficient mice. Hamaguchi-Hamada, K., Sanbo, C., Hamada, S., Yagi, T. Neurosci. Res. (2004) [Pubmed]
  9. Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. Chin, J., Palop, J.J., Puoliväli, J., Massaro, C., Bien-Ly, N., Gerstein, H., Scearce-Levie, K., Masliah, E., Mucke, L. J. Neurosci. (2005) [Pubmed]
  10. Role of Fyn tyrosine kinase in ethanol consumption by mice. Cowen, M.S., Schumann, G., Yagi, T., Spanagel, R. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  11. A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Wary, K.K., Mariotti, A., Zurzolo, C., Giancotti, F.G. Cell (1998) [Pubmed]
  12. Disruption of the csk gene, encoding a negative regulator of Src family tyrosine kinases, leads to neural tube defects and embryonic lethality in mice. Imamoto, A., Soriano, P. Cell (1993) [Pubmed]
  13. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Mukhopadhyay, D., Tsiokas, L., Zhou, X.M., Foster, D., Brugge, J.S., Sukhatme, V.P. Nature (1995) [Pubmed]
  14. Initial events of myelination involve Fyn tyrosine kinase signalling. Umemori, H., Sato, S., Yagi, T., Aizawa, S., Yamamoto, T. Nature (1994) [Pubmed]
  15. Unchanged scrapie pathology in brain tissue of tyrosine kinase Fyn-deficient mice. Schwarz, A., Burwinkel, M., Riemer, C., Schultz, J., Baier, M. Neuro-degenerative diseases. (2004) [Pubmed]
  16. Restoration of FcRgamma/Fyn signaling repairs central nervous system demyelination. Seiwa, C., Yamamoto, M., Tanaka, K., Fukutake, M., Ueki, T., Takeda, S., Sakai, R., Ishige, A., Watanabe, K., Akita, M., Yagi, T., Tanaka, K., Asou, H. J. Neurosci. Res. (2007) [Pubmed]
  17. Dynamic characteristics and adaptability of reflex eye movements of Fyn-kinase-deficient mice. Kitazawa, H., Katoh, A., Yagi, T., Nagao, S. Neurosci. Lett. (2000) [Pubmed]
  18. Itk and Fyn make independent contributions to T cell activation. Liao, X.C., Littman, D.R., Weiss, A. J. Exp. Med. (1997) [Pubmed]
  19. Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase. Sette, C., Paronetto, M.P., Barchi, M., Bevilacqua, A., Geremia, R., Rossi, P. EMBO J. (2002) [Pubmed]
  20. Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells. Li, B., Subleski, M., Fusaki, N., Yamamoto, T., Copeland, T., Princler, G.L., Kung, H., Kamata, T. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  21. Defective thymocyte maturation by transgenic expression of a truncated form of the T lymphocyte adapter molecule and Fyn substrate, Sin. Donlin, L.T., Roman, C.A., Adlam, M., Regelmann, A.G., Alexandropoulos, K. J. Immunol. (2002) [Pubmed]
  22. alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases. van Oers, N.S., Lowin-Kropf, B., Finlay, D., Connolly, K., Weiss, A. Immunity (1996) [Pubmed]
  23. NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice. Beggs, H.E., Soriano, P., Maness, P.F. J. Cell Biol. (1994) [Pubmed]
  24. A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase. Satterthwaite, A.B., Willis, F., Kanchanastit, P., Fruman, D., Cantley, L.C., Helgason, C.D., Humphries, R.K., Lowell, C.A., Simon, M., Leitges, M., Tarakhovsky, A., Tedder, T.F., Lesche, R., Wu, H., Witte, O.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  25. PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A. Tezuka, T., Umemori, H., Akiyama, T., Nakanishi, S., Yamamoto, T. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  26. Phosphorylation of Cbl following stimulation with interleukin-3 and its association with Grb2, Fyn, and phosphatidylinositol 3-kinase. Anderson, S.M., Burton, E.A., Koch, B.L. J. Biol. Chem. (1997) [Pubmed]
  27. Integrative metabolic regulation of peripheral tissue fatty acid oxidation by the SRC kinase family member Fyn. Bastie, C.C., Zong, H., Xu, J., Busa, B., Judex, S., Kurland, I.J., Pessin, J.E. Cell Metab. (2007) [Pubmed]
  28. The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation. Sun, X.J., Pons, S., Asano, T., Myers, M.G., Glasheen, E., White, M.F. J. Biol. Chem. (1996) [Pubmed]
  29. Constitutive activation of delayed-rectifier potassium channels by a src family tyrosine kinase in Schwann cells. Sobko, A., Peretz, A., Attali, B. EMBO J. (1998) [Pubmed]
  30. Functional interaction of Src family kinases with the acetylcholine receptor in C2 myotubes. Fuhrer, C., Hall, Z.W. J. Biol. Chem. (1996) [Pubmed]
  31. Interaction of p59fyn kinase with the dynein light chain, Tctex-1, and colocalization during cytokinesis. Campbell, K.S., Cooper, S., Dessing, M., Yates, S., Buder, A. J. Immunol. (1998) [Pubmed]
  32. A Novel, Non-immunogenic Fyn SH3-derived Binding Protein with Tumor Vascular Targeting Properties. Grabulovski, D., Kaspar, M., Neri, D. J. Biol. Chem. (2007) [Pubmed]
  33. Fyn associates with Cbl and phosphorylates tyrosine 731 in Cbl, a binding site for phosphatidylinositol 3-kinase. Hunter, S., Burton, E.A., Wu, S.C., Anderson, S.M. J. Biol. Chem. (1999) [Pubmed]
  34. Identification of PSD-93 as a substrate for the Src family tyrosine kinase Fyn. Nada, S., Shima, T., Yanai, H., Husi, H., Grant, S.G., Okada, M., Akiyama, T. J. Biol. Chem. (2003) [Pubmed]
  35. Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development. Arnaud, L., Ballif, B.A., Förster, E., Cooper, J.A. Curr. Biol. (2003) [Pubmed]
  36. Physical and functional interactions of protein tyrosine kinases, p59fyn and ZAP-70, in T cell signaling. Fusaki, N., Matsuda, S., Nishizumi, H., Umemori, H., Yamamoto, T. J. Immunol. (1996) [Pubmed]
  37. Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor. Nakazawa, T., Komai, S., Tezuka, T., Hisatsune, C., Umemori, H., Semba, K., Mishina, M., Manabe, T., Yamamoto, T. J. Biol. Chem. (2001) [Pubmed]
  38. Specificity of insulin-like growth factor I and insulin on Shc phosphorylation and Grb2 recruitment in caveolae. Biedi, C., Panetta, D., Segat, D., Cordera, R., Maggi, D. Endocrinology (2003) [Pubmed]
  39. Tyrosine phosphorylation and src family kinases control keratinocyte cell-cell adhesion. Calautti, E., Cabodi, S., Stein, P.L., Hatzfeld, M., Kedersha, N., Paolo Dotto, G. J. Cell Biol. (1998) [Pubmed]
  40. Protein tyrosine phosphatase alpha regulates Fyn activity and Cbp/PAG phosphorylation in thymocyte lipid rafts. Maksumova, L., Le, H.T., Muratkhodjaev, F., Davidson, D., Veillette, A., Pallen, C.J. J. Immunol. (2005) [Pubmed]
  41. Molecular cloning of a cDNA encoding a phosphoprotein, Efs, which contains a Src homology 3 domain and associates with Fyn. Ishino, M., Ohba, T., Sasaki, H., Sasaki, T. Oncogene (1995) [Pubmed]
  42. NMDA-receptor proteins are upregulated in the hippocampus of postnatal heterozygous reeler mice. Isosaka, T., Hattori, K., Yagi, T. Brain Res. (2006) [Pubmed]
  43. Fyn can partially substitute for Lck in T lymphocyte development. Groves, T., Smiley, P., Cooke, M.P., Forbush, K., Perlmutter, R.M., Guidos, C.J. Immunity (1996) [Pubmed]
  44. A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5. Yasue, T., Nishizumi, H., Aizawa, S., Yamamoto, T., Miyake, K., Mizoguchi, C., Uehara, S., Kikuchi, Y., Takatsu, K. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  45. T-cell receptor antagonists induce Vav phosphorylation by selective activation of Fyn kinase. Huang, J., Tilly, D., Altman, A., Sugie, K., Grey, H.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  46. Requirement for Src family protein tyrosine kinases in G2 for fibroblast cell division. Roche, S., Fumagalli, S., Courtneidge, S.A. Science (1995) [Pubmed]
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