proto oncogene proteins c fyn


Summary: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.

Top Publications

  1. Dose M, Gounari F. The My(c)stery of iNKT cell ontogeny. Cell Cycle. 2009;8:3082-5 pubmed
    ..We review aspects of early iNKT ontogeny in light of our findings and speculate about possible mechanistic links controlling c-Myc activity in newly selected cells. ..
  2. Li W, Febbraio M, Reddy S, Yu D, Yamamoto M, Silverstein R. CD36 participates in a signaling pathway that regulates ROS formation in murine VSMCs. J Clin Invest. 2010;120:3996-4006 pubmed publisher
    ..These data suggest that CD36-mediated downregulation of antioxidant systems in VSMCs may contribute to its prothrombotic, proinflammatory, and atherogenic effects. ..
  3. Kohn J, Gillespie B, Plaxco K. Non-sequence-specific interactions can account for the compaction of proteins unfolded under "native" conditions. J Mol Biol. 2009;394:343-50 pubmed publisher
  4. Lim S, Kwon S, Lee M, Moon J, Jeong D, Park E, et al. Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn. EMBO J. 2009;28:3564-78 pubmed publisher
  5. Harita Y, Kurihara H, Kosako H, Tezuka T, Sekine T, Igarashi T, et al. Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1. J Biol Chem. 2009;284:8951-62 pubmed publisher
    ..Given the profound effect of PLC-gamma in diverse cellular functions, regulation of the Ca(2+) signaling by Nephrin may be important in modulating the glomerular filtration barrier function. ..
  6. Mamchak A, Thien C, Dagger S, Lyandres J, Jiang S, Langdon W, et al. Unaltered negative selection and Treg development of self-reactive thymocytes in TCR transgenic Fyn-deficient mice. Eur J Immunol. 2010;40:539-47 pubmed publisher
    ..Combined, these data indicate that Fyn was not required for the induction of central tolerance by negative selection, the adaptor protein role of c-Cbl, or the normal development and function of Treg. ..
  7. Kovalovsky D, ALONZO E, Uche O, Eidson M, Nichols K, Sant Angelo D. PLZF induces the spontaneous acquisition of memory/effector functions in T cells independently of NKT cell-related signals. J Immunol. 2010;184:6746-55 pubmed publisher
    ..These data show that PLZF is sufficient to promote T cell effector functions and that PLZF acts independently of SAP- and Fyn-mediated signaling pathways. ..
  8. Denisov A, Kloser E, Gray D, Mittermaier A. Protein alignment using cellulose nanocrystals: practical considerations and range of application. J Biomol NMR. 2010;47:195-204 pubmed publisher
    ..Using the SH3 domain from the Fyn tyrosine kinase as a model system, we find that CNCs produce an alignment frame collinear with that of the commonly used Pf1 bacteriophage alignment medium, but of opposite magnitude. ..
  9. Dang D, Sadler S, Ramos D. Modulation of EGFR by oral squamous cell carcinoma cell lines. J Calif Dent Assoc. 2009;37:869-74 pubmed
    ..The authors suggest perhaps targeting both alphanubeta6 and EGFR may provide additional benefits. ..

More Information


  1. Hager E, Hawwari A, Matsuda J, Krangel M, Gapin L. Multiple constraints at the level of TCRalpha rearrangement impact Valpha14i NKT cell development. J Immunol. 2007;179:2228-34 pubmed
    ..Altogether, this study provides evidence that there is no directed rearrangement of Valpha14 to Jalpha18 segments and supports the instructive selection model for NKT cell selection. ..
  2. Chari R, Kim S, Murugappan S, Sanjay A, Daniel J, Kunapuli S. Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule secretion. Blood. 2009;114:3056-63 pubmed publisher
    ..Therefore, we conclude that Lyn-mediated phosphorylations of PKC-delta and SHIP-1 and their associations negatively regulate GPVI-mediated dense granule secretion in platelets. ..
  3. Salmond R, Emery J, Okkenhaug K, Zamoyska R. MAPK, phosphatidylinositol 3-kinase, and mammalian target of rapamycin pathways converge at the level of ribosomal protein S6 phosphorylation to control metabolic signaling in CD8 T cells. J Immunol. 2009;183:7388-97 pubmed publisher
    ..These results place rpS6 phosphorylation as a point of convergence for multiple crucial signaling pathways downstream of TCR triggering. ..
  4. Kao T, Palmesino E, Kania A. SRC family kinases are required for limb trajectory selection by spinal motor axons. J Neurosci. 2009;29:5690-700 pubmed publisher
    ..In summary, our findings demonstrate that SFKs are essential for motor axon guidance and suggest that they play an important role in relaying ephrin:Eph signals that mediate the selection of motor axon trajectory in the limb. ..
  5. Luo J, McGinnis L, Kinsey W. Fyn kinase activity is required for normal organization and functional polarity of the mouse oocyte cortex. Mol Reprod Dev. 2009;76:819-31 pubmed publisher
    ..This was associated with a delay in completion of meiosis II. Pronuclei, however, eventually formed and subsequent mitotic cleavages and blastocyst formation occurred normally. ..
  6. Nemec A, Zubritsky L, Barchowsky A. Chromium(VI) stimulates Fyn to initiate innate immune gene induction in human airway epithelial cells. Chem Res Toxicol. 2010;23:396-404 pubmed publisher
    ..These data support a novel mechanism through which Cr(VI) stimulates Fyn to initiate interferon-like signaling for STAT1-dependent gene transactivation. ..
  7. Wright B, Moraes L, Kemp C, Mullen W, Crozier A, Lovegrove J, et al. A structural basis for the inhibition of collagen-stimulated platelet function by quercetin and structurally related flavonoids. Br J Pharmacol. 2010;159:1312-25 pubmed publisher
    ..The structure-activity relationship for flavonoids on platelet function presented here may be exploited to design selective inhibitors of cell signalling. ..
  8. Chan M, Gigliotti N, Matangkasombut P, Gauld S, Cambier J, Rosenwasser L. CD23-mediated cell signaling in human B cells differs from signaling in cells of the monocytic lineage. Clin Immunol. 2010;137:330-6 pubmed publisher
    ..Activation of the tyrosine kinase Fyn and the serine/threonine kinase Akt were only observed in B cells. These results suggest that the CD23-mediated signal transduction pathways in human B cells and human monocytes are different. ..
  9. Perez M, Ortiz E, Roffe M, Soto E, Pasquini J. Fyn kinase is involved in oligodendroglial cell differentiation induced by apotransferrin. J Neurosci Res. 2009;87:3378-89 pubmed publisher
    ..These results give support to our hypothesis that Fyn kinase plays a key role in the differentiation process of OLGcs promoted by aTf. ..
  10. Demers A, Caron V, Rodrigue Way A, Wahli W, Ong H, Tremblay A. A concerted kinase interplay identifies PPARgamma as a molecular target of ghrelin signaling in macrophages. PLoS ONE. 2009;4:e7728 pubmed publisher
    ..Collectively, these results illustrate a complex interplay involving Fyn/Dok-1/Erk and Galphaq/PI3-K/Akt pathways to transduce in a concerted manner responsiveness of PPARgamma to ghrelin in macrophages. ..
  11. Rahman M, Senga T, Ito S, Hyodo T, Hasegawa H, Hamaguchi M. S-nitrosylation at cysteine 498 of c-Src tyrosine kinase regulates nitric oxide-mediated cell invasion. J Biol Chem. 2010;285:3806-14 pubmed publisher
    ..These results identify a novel signaling pathway that links NO and Src family kinases to cancer cell invasion and metastasis. ..
  12. Murata Y, Mori M, Kotani T, Supriatna Y, Okazawa H, Kusakari S, et al. Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatases and their complex formations with Grb2 or Fyn. Genes Cells. 2010;15:513-24 pubmed publisher
    ..Our results thus suggest that tyrosine phosphorylation of R3 subtype RPTPs promotes their complex formations with Grb2 or Fyn and thus participates in the regulation of cell morphology. ..
  13. Luo J, McGinnis L, Kinsey W. Role of Fyn kinase in oocyte developmental potential. Reprod Fertil Dev. 2010;22:966-76 pubmed publisher
    ..These defects cause developmental arrest during oocyte maturation and pronuclear congression. ..
  14. Hossain S, Fragoso G, Mushynski W, Almazan G. Regulation of peripheral myelination by Src-like kinases. Exp Neurol. 2010;226:47-57 pubmed publisher
    ..PP2 blocked the phosphorylation of all three kinases. Our results support a role for SLKs in the initiation of peripheral myelination via the activation of p38, Akt and ERK, which regulate Krox-20 expression and peripheral myelination. ..
  15. Greenberger S, Levanon E, Paz Yaacov N, Barzilai A, Safran M, Osenberg S, et al. Consistent levels of A-to-I RNA editing across individuals in coding sequences and non-conserved Alu repeats. BMC Genomics. 2010;11:608 pubmed publisher
    ..Our findings suggest that A-to-I RNA-editing of Alu elements is a tightly regulated process and, as such, might have been recruited in the course of primate evolution for post-transcriptional regulatory mechanisms. ..
  16. Lenaerts T, Schymkowitz J, Rousseau F. Protein domains as information processing units. Curr Protein Pept Sci. 2009;10:133-45 pubmed
  17. Lam B, Zhang W, Enticknap N, Haggis E, Cader M, Chawla S. Inverse regulation of plasticity-related immediate early genes by calcineurin in hippocampal neurons. J Biol Chem. 2009;284:12562-71 pubmed publisher
    ..Conversely, SRE-mediated c-fos induction in the absence of a functional CRE was enhanced by calcineurin inhibitors. Our experiments thus implicate calcineurin as a negative regulator of SRE-dependent neuronal genes. ..
  18. Hsu K, Fan H, Chen Y, Huang Y, Chen C, Wu J, et al. Protein kinase C-Fyn kinase cascade mediates the oleic acid-induced disassembly of neonatal rat cardiomyocyte adherens junctions. Int J Biochem Cell Biol. 2009;41:1536-46 pubmed publisher
    ..Therefore, inhibitors of PKC-alpha/-epsilon and Src family kinase are potential candidates as cardioprotection agents against OA-induced heart injury during ischemia-reperfusion. ..
  19. Laursen L, Chan C, Ffrench Constant C. An integrin-contactin complex regulates CNS myelination by differential Fyn phosphorylation. J Neurosci. 2009;29:9174-85 pubmed publisher
    ..We conclude, therefore, that a novel integrin/contactin complex coordinates signals from extracellular matrix and the axonal surface to regulate both oligodendrocyte survival and myelination by controlling Fyn activity. ..
  20. Boivin D, Labbe D, Fontaine N, Lamy S, Beaulieu E, Gingras D, et al. The stem cell marker CD133 (prominin-1) is phosphorylated on cytoplasmic tyrosine-828 and tyrosine-852 by Src and Fyn tyrosine kinases. Biochemistry. 2009;48:3998-4007 pubmed publisher
    ..Identification of CD133 as a substrate for Src-family tyrosine kinases suggests that the cytoplasmic domain of CD133 might play an important role in the regulation of its functions. ..
  21. Sun J, Hopkins B, Tsujikawa K, Perruzzi C, Adini I, Swerlick R, et al. Thrombospondin-1 modulates VEGF-A-mediated Akt signaling and capillary survival in the developing retina. Am J Physiol Heart Circ Physiol. 2009;296:H1344-51 pubmed publisher
  22. Sanchez Miranda E, Ibarra Sanchez A, Gonzalez Espinosa C. Fyn kinase controls FcepsilonRI receptor-operated calcium entry necessary for full degranulation in mast cells. Biochem Biophys Res Commun. 2010;391:1714-20 pubmed publisher
    ..Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in FcepsilonRI-stimulated mast cells. ..
  23. Audard V, Zhang S, Copie Bergman C, Rucker Martin C, Ory V, Candelier M, et al. Occurrence of minimal change nephrotic syndrome in classical Hodgkin lymphoma is closely related to the induction of c-mip in Hodgkin-Reed Sternberg cells and podocytes. Blood. 2010;115:3756-62 pubmed publisher
    ..Moreover, we showed that c-mip was up-regulated in Fyn-deficient podocytes. c-mip may be a useful marker of cHL-MCNS and its induction reflects the dysregulation of proximal signaling. ..
  24. Bennett M. Positive and negative symptoms in schizophrenia: the NMDA receptor hypofunction hypothesis, neuregulin/ErbB4 and synapse regression. Aust N Z J Psychiatry. 2009;43:711-21 pubmed publisher
  25. Suzuki R, Liu X, Olivera A, Aguiniga L, Yamashita Y, Blank U, et al. Loss of TRPC1-mediated Ca2+ influx contributes to impaired degranulation in Fyn-deficient mouse bone marrow-derived mast cells. J Leukoc Biol. 2010;88:863-75 pubmed publisher
    ..This demonstrates that in addition to a role described previously for Orai1 in promoting MC degranulation, nonselective cation channels participate in promoting the exocytotic response. ..
  26. Brignatz C, Paronetto M, Opi S, Cappellari M, Audebert S, Feuillet V, et al. Alternative splicing modulates autoinhibition and SH3 accessibility in the Src kinase Fyn. Mol Cell Biol. 2009;29:6438-48 pubmed publisher
    ..Our results illustrate a novel mechanism of evolution that may contribute to the complexity of Src kinase regulation. ..
  27. Riento K, Frick M, Schafer I, Nichols B. Endocytosis of flotillin-1 and flotillin-2 is regulated by Fyn kinase. J Cell Sci. 2009;122:912-8 pubmed publisher
    ..Uptake of the GPI-linked protein CD59 is reduced by expression of the phenylalanine-mutated flotillins. These data establish uptake of flotillin microdomains as a tyrosine-kinase-regulated endocytic process. ..
  28. Wang J, Lanfranco M, Gibb S, Yowell Q, Carnicella S, Ron D. Long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum play a crucial role in alcohol consumption and relapse. J Neurosci. 2010;30:10187-98 pubmed publisher
    ..Our results suggest that the upregulation of NR2B-NMDAR activity within the DMS by alcohol contributes to the maladaptive synaptic changes that lead to excessive alcohol intake and relapse. ..
  29. Ittner L, Ke Y, Delerue F, Bi M, Gladbach A, van Eersel J, et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell. 2010;142:387-97 pubmed publisher
    ..Our findings suggest that this dendritic role of tau confers Abeta toxicity at the postsynapse with direct implications for pathogenesis and treatment of AD. ..
  30. García Román J, Ibarra Sanchez A, Lamas M, Gonzalez Espinosa C. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells. Biochem Biophys Res Commun. 2010;401:262-7 pubmed publisher
    ..Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals-dependent Fyn kinase activation. ..
  31. Saito Y, Jensen A, Salgia R, Posadas E. Fyn: a novel molecular target in cancer. Cancer. 2010;116:1629-37 pubmed publisher
    ..As several agents in clinical development affect Fyn activation, understanding the role that Fyn plays in cancer is of great importance in oncology. Cancer 2010. (c) 2010 American Cancer Society. ..
  32. Lin Y, Huang J, Kan H, Frisbee J, Yu H. Rescue of a trafficking defective human pacemaker channel via a novel mechanism: roles of Src, Fyn, and Yes tyrosine kinases. J Biol Chem. 2009;284:30433-40 pubmed publisher
    ..In conclusion, we demonstrate a novel mechanism using three endogenous Src kinases to rescue a trafficking defective HCN4 mutant channel (D553N) by enhancing the tyrosine phosphorylation of the mutant channel protein. ..
  33. Chen S, Khanna R, Bessette D, Samayawardhena L, Pallen C. Protein tyrosine phosphatase-alpha complexes with the IGF-I receptor and undergoes IGF-I-stimulated tyrosine phosphorylation that mediates cell migration. Am J Physiol Cell Physiol. 2009;297:C133-9 pubmed publisher
  34. Girasol A, Albuquerque G, Mansour E, Araujo E, Degasperi G, Denis R, et al. Fyn mediates leptin actions in the thymus of rodents. PLoS ONE. 2009;4:e7707 pubmed publisher
    ..Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue. ..
  35. Vatish M, Yamada E, Pessin J, Bastie C. Fyn kinase function in lipid utilization: a new upstream regulator of AMPK activity?. Arch Physiol Biochem. 2009;115:191-8 pubmed publisher
    ..In this review, we present novel evidence of crosstalk between Fyn, one member of the Src kinase family, and AMPK. ..
  36. McPherson V, Sharma N, Everingham S, Smith J, Zhu H, Feng G, et al. SH2 domain-containing phosphatase-2 protein-tyrosine phosphatase promotes Fc epsilon RI-induced activation of Fyn and Erk pathways leading to TNF alpha release from bone marrow-derived mast cells. J Immunol. 2009;183:4940-7 pubmed publisher
    ..Overall, our study identifies SHP2 as a positive effector of Fc(epsilon)RI-induced activation of Fyn/Grb2-associated binder 2/Akt and Ras/Erk pathways leading to TNF-alpha release from mast cells. ..
  37. Laird R, Hayes S. Roles of the Src tyrosine kinases Lck and Fyn in regulating gammadeltaTCR signal strength. PLoS ONE. 2010;5:e8899 pubmed publisher
    ..These results indicate that the cellular levels of Lck and Fyn play a role in regulating the strength of the gammadeltaTCR signaling response at different stages in the life of the gammadelta T cell. ..
  38. McGinnis L, Albertini D. Dynamics of protein phosphorylation during meiotic maturation. J Assist Reprod Genet. 2010;27:169-82 pubmed publisher
    ..The findings indicate that distinct signaling pathways mediate nuclear and cytoplasmic maturation during in vitro maturation in a fashion consistent with a role for tyrosine kinases in cortical maturation and oocyte quality. ..
  39. Pastor I, Laso F, Inés S, Marcos M, Gonzalez Sarmiento R. Genetic association between -93A/G polymorphism in the Fyn kinase gene and alcohol dependence in Spanish men. Eur Psychiatry. 2009;24:191-4 pubmed publisher
    ..9% vs 30.6%; p=0.015; OR=2.077; 95% CI 1.165-3.704). Our results show that the -93G allele of Fyn kinase gene is associated with higher risk to develop alcohol dependence in Spanish men. ..
  40. Jurd R, Tretter V, Walker J, Brandon N, Moss S. Fyn kinase contributes to tyrosine phosphorylation of the GABA(A) receptor gamma2 subunit. Mol Cell Neurosci. 2010;44:129-34 pubmed publisher
    ..This has important implications for the regulation of synaptic GABA(A) receptors via signaling pathways that lead to the activation of Fyn kinase. ..
  41. Barbu E, Zhang J, Siraganian R. The limited contribution of Fyn and Gab2 to the high affinity IgE receptor signaling in mast cells. J Biol Chem. 2010;285:15761-8 pubmed publisher
  42. Samayawardhena L, Pallen C. PTPalpha activates Lyn and Fyn and suppresses Hck to negatively regulate FcepsilonRI-dependent mast cell activation and allergic responses. J Immunol. 2010;185:5993-6002 pubmed publisher
    ..Furthermore, the findings indicate that hyperactivation of PTP?(-/-) mast cells and enhanced IgE-dependent allergic responses of PTP?(-/-) mice are due to the ablated function of PTP? as a critical regulator of Lyn negative signaling. ..
  43. Szczepankiewicz A, Rybakowski J, Skibinska M, Dmitrzak Weglarz M, Leszczynska Rodziewicz A, Wilkosc M, et al. FYN kinase gene: another glutamatergic gene associated with bipolar disorder?. Neuropsychobiology. 2009;59:178-83 pubmed publisher
    ..86, D' = 0.93 with 95% CI = 0.9-0.97). The results suggest that the glutamatergic FYN gene may be associated with bipolar disorder, particularly with type I illness and early age of onset. ..
  44. Relucio J, Tzvetanova I, Ao W, Lindquist S, Colognato H. Laminin alters fyn regulatory mechanisms and promotes oligodendrocyte development. J Neurosci. 2009;29:11794-806 pubmed publisher
  45. Lin S, Zarrine Afsar A, Davidson A. The osmolyte trimethylamine-N-oxide stabilizes the Fyn SH3 domain without altering the structure of its folding transition state. Protein Sci. 2009;18:526-36 pubmed publisher
    ..Through thermodynamic analysis of mutants, we also discovered that the stabilizing effect of TMAO is lessened with increasing temperature. ..
  46. Zhou Y, Jiang D, Thomason D, Jarrett H. Laminin-induced activation of Rac1 and JNKp46 is initiated by Src family kinases and mimics the effects of skeletal muscle contraction. Biochemistry. 2007;46:14907-16 pubmed
    ..The DGC likely represents a mechanoreceptor in skeletal muscle-regulating muscle growth in response to muscle activity. Src family kinases play an initiating and critical role. ..
  47. Rawat A, Nagaraj R. Determinants of membrane association in the SH4 domain of Fyn: roles of N-terminus myristoylation and side-chain thioacylation. Biochim Biophys Acta. 2010;1798:1854-63 pubmed publisher
  48. Demers J, Mittermaier A. Binding mechanism of an SH3 domain studied by NMR and ITC. J Am Chem Soc. 2009;131:4355-67 pubmed publisher
    ..The combination of NMR and ITC data sheds light on how the Fyn tyrosine kinase is activated by binding to proline-rich targets, and represents a powerful approach for characterizing transient protein/ligand interactions. ..
  49. Zhang S, Kamal M, Dahan K, Pawlak A, Ory V, Desvaux D, et al. c-mip impairs podocyte proximal signaling and induces heavy proteinuria. Sci Signal. 2010;3:ra39 pubmed publisher
    ..Together, these results identify c-mip as a key component in the molecular pathogenesis of acquired podocyte diseases. ..
  50. Namekata K, Harada C, Taya C, Guo X, Kimura H, Parada L, et al. Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex. Proc Natl Acad Sci U S A. 2010;107:7586-91 pubmed publisher
    ..Our results highlight a unique mechanism through which Dock-GEFs achieve spatial and temporal restriction of WAVE signaling, and identify Dock-GEF activity as a potential therapeutic target for axonal regeneration. ..
  51. Takizawa H, Nishimura S, Takayama N, Oda A, Nishikii H, Morita Y, et al. Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo. J Clin Invest. 2010;120:179-90 pubmed publisher
    ..Outside-in signaling modulators could represent new therapeutic targets for the prevention of cardiovascular events. ..
  52. Levi M, Shalgi R. The role of Fyn kinase in the release from metaphase in mammalian oocytes. Mol Cell Endocrinol. 2010;314:228-33 pubmed publisher
    ..Altogether, Fyn is suggested to play an essential role in signaling events that implicate SAC pathway and hence in regulating the exit from metaphase in oocytes and zygote. ..
  53. Pena F, Ordaz B, Balleza Tapia H, Bernal Pedraza R, Márquez Ramos A, Carmona Aparicio L, et al. Beta-amyloid protein (25-35) disrupts hippocampal network activity: role of Fyn-kinase. Hippocampus. 2010;20:78-96 pubmed publisher
    ..We propose that such alteration might be related to the cognitive impairment observed, at least, during the early phases of Alzheimer's disease. ..