Tyrosinkinase Fyn

Tyrosinkinase Fyn

Tyrosinkinase Fyn

Eigenschaften des menschlichen Proteins
Masse/Länge Primärstruktur 537 Aminosäuren
Kofaktor Mn2+
Isoformen B, T, P06421-3
Bezeichner
Gen-Name FYN
Externe IDs OMIM: 137025 UniProt: P06241
Enzymklassifikation
EC, Kategorie 2.7.10.2 Tyrosinkinase
Reaktionsart Phosphorylierung von Tyrosinresten in Proteinen
Substrat Xaa-Tyr-Yaa + ATP
Produkte Xaa-TyrP-Yaa + ADP
Vorkommen
Übergeordnetes Taxon Wirbeltiere[1]

Die Tyrosinkinase Fyn ist ein Enzym in Wirbeltieren, das die Phosphorylierung mehrerer Proteine an der Aminosäure Tyrosin katalysiert (Tyrosinkinase). Diese Reaktion ist Teil von etwa einem Dutzend Signalwege, die unentbehrlich für die Embryonalentwicklung des Gehirns und dessen spätere Funktion sind. Beim Mensch kontrolliert Fyn das Wachstum der Axone und den Calciumgehalt von Zellen. Von den drei bekannten Isoformen wird 'B' besonders im Gehirn und 'T' in T-Zellen exprimiert.[2]

Interaktionen

Für FYN wurden einige Interaktionen mit anderen Proteinen nachgewiesen.

Literatur

Quellen, Zitatnachweise, Zeitschriftenartikel

  1. Orthologe bei OMA
  2. UniProt P06421
  3. T Shima, Okumura N, Takao T, Satomi Y, Yagi T, Okada M, Nagai K: Interaction of the SH2 domain of Fyn with a cytoskeletal protein, beta-adducin. In: J. Biol. Chem.. 276, Nr. 45, United States, November 2001, S. 42233–40. doi:10.1074/jbc.M102699200. PMID 11526103.
  4. 4,0 4,1 Corinna Klein, Kramer Eva-Maria, Cardine Anne-Marie, Schraven Burkhardt, Brandt Roland, Trotter Jacqueline: Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau. In: J. Neurosci.. 22, Nr. 3, United States, Februar 2002, S. 698–707. PMID 11826099.
  5. J C Donaldson, Dempsey P J, Reddy S, Bouton A H, Coffey R J, Hanks S K: Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells. In: Exp. Cell Res.. 256, Nr. 1, UNITED STATES, April 2000, S. 168–78. doi:10.1006/excr.2000.4822. PMID 10739664.
  6. S N Manié, Astier A, Haghayeghi N, Canty T, Druker B J, Hirai H, Freedman A S: Regulation of integrin-mediated p130(Cas) tyrosine phosphorylation in human B cells. A role for p59(Fyn) and SHP2. In: J. Biol. Chem.. 272, Nr. 25, UNITED STATES, Juni 1997, S. 15636–41. doi:10.1074/jbc.272.25.15636. PMID 9188452.
  7. Taher E I Taher, Tjin Esther P M, Beuling Esther A, Borst Jannie, Spaargaren Marcel, Pals Steven T: c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination. In: J. Immunol.. 169, Nr. 7, United States, Oktober 2002, S. 3793–800. PMID 12244174.
  8. 8,0 8,1 M Deckert, Elly C, Altman A, Liu Y C: Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases. In: J. Biol. Chem.. 273, Nr. 15, UNITED STATES, April 1998, S. 8867–74. doi:10.1074/jbc.273.15.8867. PMID 9535867.
  9. M Kim, Tezuka T, Suziki Y, Sugano S, Hirai M, Yamamoto T: Molecular cloning and characterization of a novel cbl-family gene, cbl-c. In: Gene. 239, Nr. 1, NETHERLANDS, Oktober 1999, S. 145–54. doi:10.1016/S0378-1119(99)00356-X. PMID 10571044.
  10. M M Huang, Bolen J B, Barnwell J W, Shattil S J, Brugge J S: Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets. In: Proc. Natl. Acad. Sci. U.S.A.. 88, Nr. 17, UNITED STATES, September 1991, S. 7844–8. doi:10.1073/pnas.88.17.7844. PMID 1715582. Volltext bei PMC: 52400.
  11. H A Bull, Brickell P M, Dowd P M: Src-related protein tyrosine kinases are physically associated with the surface antigen CD36 in human dermal microvascular endothelial cells. In: FEBS Lett.. 351, Nr. 1, NETHERLANDS, August 1994, S. 41–4. doi:10.1016/0014-5793(94)00814-0. PMID 7521304.
  12. S Ilangumaran, Briol A, Hoessli D C: CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes. In: Blood. 91, Nr. 10, UNITED STATES, May. 1998, S. 3901–8. PMID 9573028.
  13. 13,0 13,1 Jose Piedra, Miravet Susana, Castaño Julio, Pálmer Héctor G, Heisterkamp Nora, García de Herreros Antonio, Duñach Mireia: p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction. In: Mol. Cell. Biol.. 23, Nr. 7, United States, April 2003, S. 2287–97. doi:10.1128/MCB.23.7.2287-2297.2003. PMID 12640114. Volltext bei PMC: 150740.
  14. T Kihara, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A: alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. In: J. Biol. Chem.. 276, Nr. 17, United States, April 2001, S. 13541–6. doi:10.1074/jbc.M008035200. PMID 11278378.
  15. S A Courtneidge, Dhand R, Pilat D, Twamley G M, Waterfield M D, Roussel M F: Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor. In: EMBO J.. 12, Nr. 3, ENGLAND, März 1993, S. 943–50. PMID 7681396. Volltext bei PMC: 413295.
  16. V Cleghon, Morrison D K: Raf-1 interacts with Fyn and Src in a non-phosphotyrosine-dependent manner. In: J. Biol. Chem.. 269, Nr. 26, UNITED STATES, Juli 1994, S. 17749–55. PMID 7517401.
  17. Maria Cruz Martinez, Ochiishi Tomoyo, Majewski Michael, Kosik Kenneth S: Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho. In: J. Cell Biol.. 162, Nr. 1, United States, Juli 2003, S. 99–111. doi:10.1083/jcb.200211025. PMID 12835311. Volltext bei PMC: 2172717.
  18. 18,0 18,1 T Tezuka, Umemori H, Akiyama T, Nakanishi S, Yamamoto T: PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A. In: Proc. Natl. Acad. Sci. U.S.A.. 96, Nr. 2, UNITED STATES, Januar 1999, S. 435–40. doi:10.1073/pnas.96.2.435. PMID 9892651. Volltext bei PMC: 15154.
  19. 19,0 19,1 Xiao-Yu Hou, Zhang Guang-Yi, Yan Jing-Zhi, Chen Min, Liu Yong: Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia. In: Brain Res.. 955, Nr. 1-2, Netherlands, November 2002, S. 123–32. doi:10.1016/S0006-8993(02)03376-0. PMID 12419528.
  20. F Sotgia, Lee H, Bedford M T, Petrucci T, Sudol M, Lisanti M P: Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins. In: Biochemistry. 40, Nr. 48, United States, Dezember 2001, S. 14585–92. doi:10.1021/bi011247r. PMID 11724572.
  21. S Choi, Park S: Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity. In: Oncogene. 18, Nr. 39, ENGLAND, September 1999, S. 5413–22. doi:10.1038/sj.onc.1202917. PMID 10498895.
  22. J Wenzel, Sanzenbacher R, Ghadimi M, Lewitzky M, Zhou Q, Kaplan D R, Kabelitz D, Feller S M, Janssen O: Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor. In: FEBS Lett.. 509, Nr. 2, Netherlands, Dezember 2001, S. 255–62. doi:10.1016/S0014-5793(01)03174-X. PMID 11741599.
  23. M Hane, Lowin B, Peitsch M, Becker K, Tschopp J: Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain. In: FEBS Lett.. 373, Nr. 3, NETHERLANDS, Oktober 1995, S. 265–8. doi:10.1016/0014-5793(95)01051-F. PMID 7589480.
  24. A J da Silva, Janssen O, Rudd C E: T cell receptor zeta/CD3-p59fyn(T)-associated p120/130 binds to the SH2 domain of p59fyn(T). In: J. Exp. Med.. 178, Nr. 6, UNITED STATES, Dezember 1993, S. 2107–13. doi:10.1084/jem.178.6.2107. PMID 7504057. Volltext bei PMC: 2191307.
  25. 25,0 25,1 A Marie-Cardine, Hendricks-Taylor L R, Boerth N J, Zhao H, Schraven B, Koretzky G A: Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130. In: J. Biol. Chem.. 273, Nr. 40, UNITED STATES, Oktober 1998, S. 25789–95. doi:10.1074/jbc.273.40.25789. PMID 9748251.
  26. Rami Yaka, He Dao-Yao, Phamluong Khanhky, Ron Dorit: Pituitary adenylate cyclase-activating polypeptide (PACAP(1-38)) enhances N-methyl-D-aspartate receptor function and brain-derived neurotrophic factor expression via RACK1. In: J. Biol. Chem.. 278, Nr. 11, United States, März 2003, S. 9630–8. doi:10.1074/jbc.M209141200. PMID 12524444.
  27. Rami Yaka, Thornton Claire, Vagts Alicia J, Phamluong Khanhky, Bonci Antonello, Ron Dorit: NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. In: Proc. Natl. Acad. Sci. U.S.A.. 99, Nr. 8, United States, April 2002, S. 5710–5. doi:10.1073/pnas.062046299. PMID 11943848. Volltext bei PMC: 122836.
  28. Juan Ma, Zhang Guang-Yi: Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia. In: Neurosci. Lett.. 348, Nr. 3, Ireland, September 2003, S. 185–9. doi:10.1016/S0304-3940(03)00784-5. PMID 12932824.
  29. N Takagi, Cheung H H, Bissoon N, Teves L, Wallace M C, Gurd J W: The effect of transient global ischemia on the interaction of Src and Fyn with the N-methyl-D-aspartate receptor and postsynaptic densities: possible involvement of Src homology 2 domains. In: J. Cereb. Blood Flow Metab.. 19, Nr. 8, UNITED STATES, August 1999, S. 880–8. doi:10.1097/00004647-199908000-00007. PMID 10458595.
  30. S C Bunnell, Diehn M, Yaffe M B, Findell P R, Cantley L C, Berg L J: Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade. In: J. Biol. Chem.. 275, Nr. 3, UNITED STATES, Januar 2000, S. 2219–30. doi:10.1074/jbc.275.3.2219. PMID 10636929.
  31. S C Bunnell, Henry P A, Kolluri R, Kirchhausen T, Rickles R J, Berg L J: Identification of Itk/Tsk Src homology 3 domain ligands. In: J. Biol. Chem.. 271, Nr. 41, UNITED STATES, Oktober 1996, S. 25646–56. doi:10.1074/jbc.271.41.25646. PMID 8810341.
  32. P P Sayeski, Ali M S, Safavi A, Lyles M, Kim S O, Frank S J, Bernstein K E: A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn. In: J. Biol. Chem.. 274, Nr. 46, UNITED STATES, November 1999, S. 33131–42. doi:10.1074/jbc.274.46.33131. PMID 10551884.
  33. Chitose Oneyama, Nakano Hirofumi, Sharma Sreenath V: UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug. In: Oncogene. 21, Nr. 13, England, März 2002, S. 2037–50. doi:10.1038/sj.onc.1205271. PMID 11960376.
  34. N Fusaki, Iwamatsu A, Iwashima M, Fujisawa J i: Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling. In: J. Biol. Chem.. 272, Nr. 10, UNITED STATES, März 1997, S. 6214–9. doi:10.1074/jbc.272.10.6214. PMID 9045636.
  35. Juhani Lahdenperä, Kilpeläinen Pekka, Liu Xiao Li, Pikkarainen Timo, Reponen Paula, Ruotsalainen Vesa, Tryggvason Karl: Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases. In: Kidney Int.. 64, Nr. 2, United States, August 2003, S. 404–13. doi:10.1046/j.1523-1755.2003.00097.x. PMID 12846735.
  36. Rakesh Verma, Wharram Bryan, Kovari Iulia, Kunkel Robin, Nihalani Deepak, Wary Kishore K, Wiggins Roger C, Killen Paul, Holzman Lawrence B: Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin. In: J. Biol. Chem.. 278, Nr. 23, United States, Juni 2003, S. 20716–23. doi:10.1074/jbc.M301689200. PMID 12668668.
  37. T Brdicka, Pavlistová D, Leo A, Bruyns E, Korínek V, Angelisová P, Scherer J, Shevchenko A, Hilgert I, Cerný J, Drbal K, Kuramitsu Y, Kornacker B, Horejsí V, Schraven B: Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. In: J. Exp. Med.. 191, Nr. 9, UNITED STATES, May. 2000, S. 1591–604. doi:10.1084/jem.191.9.1591. PMID 10790433. Volltext bei PMC: 2213442.
  38. I Gout, Dhand R, Panayotou G, Fry M J, Hiles I, Otsu M, Waterfield M D: Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system. In: Biochem. J.. 288 ( Pt 2), ENGLAND, Dezember 1992, S. 395–405. PMID 1334406. Volltext bei PMC: 1132024.
  39. D Ron, Napolitano E W, Voronova A, Vasquez N J, Roberts D N, Calio B L, Caothien R H, Pettiford S M, Wellik S, Mandac J B, Kauvar L M: Direct interaction in T-cells between thetaPKC and the tyrosine kinase p59fyn. In: J. Biol. Chem.. 274, Nr. 27, UNITED STATES, Juli 1999, S. 19003–10. doi:10.1074/jbc.274.27.19003. PMID 10383400.
  40. Magdalena M Gorska, Stafford Susan J, Cen Osman, Sur Sanjiv, Alam Rafeul: Unc119, a novel activator of Lck/Fyn, is essential for T cell activation. In: J. Exp. Med.. 199, Nr. 3, United States, Februar 2004, S. 369–79. PMID 14757743. Volltext bei PMC: 2211793.
  41. Samantha Messina, Onofri Franco, Bongiorno-Borbone Lucilla, Giovedì Silvia, Valtorta Flavia, Girault Jean-Antoine, Benfenati Fabio: Specific interactions of neuronal focal adhesion kinase isoforms with Src kinases and amphiphysin. In: J. Neurochem.. 84, Nr. 2, England, Januar 2003, S. 253–65. doi:10.1046/j.1471-4159.2003.01519.x. PMID 12558988.
  42. S T Arold, Ulmer T S, Mulhern T D, Werner J M, Ladbury J E, Campbell I D, Noble M E: The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases. In: J. Biol. Chem.. 276, Nr. 20, United States, May. 2001, S. 17199–205. doi:10.1074/jbc.M011185200. PMID 11278857.
  43. R K Ganju, Hatch W C, Avraham H, Ona M A, Druker B, Avraham S, Groopman J E: RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes. In: J. Exp. Med.. 185, Nr. 6, UNITED STATES, März 1997, S. 1055–63. doi:10.1084/jem.185.6.1055. PMID 9091579. Volltext bei PMC: 2196239.
  44. T Katagiri, Takahashi T, Sasaki T, Nakamura S, Hattori S: Protein-tyrosine kinase Pyk2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402. In: J. Biol. Chem.. 275, Nr. 26, UNITED STATES, Juni 2000, S. 19645–52. doi:10.1074/jbc.M909828199. PMID 10867021.
  45. D Qian, Lev S, van Oers N S, Dikic I, Schlessinger J, Weiss A: Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling. In: J. Exp. Med.. 185, Nr. 7, UNITED STATES, April 1997, S. 1253–9. doi:10.1084/jem.185.7.1253. PMID 9104812. Volltext bei PMC: 2196260.
  46. Sachiko Taniguchi, Liu Hui, Nakazawa Takanobu, Yokoyama Kazumasa, Tezuka Tohru, Yamamoto Tadashi: p250GAP, a neural RhoGAP protein, is associated with and phosphorylated by Fyn. In: Biochem. Biophys. Res. Commun.. 306, Nr. 1, United States, Juni 2003, S. 151–5. doi:10.1016/S0006-291X(03)00923-9. PMID 12788081.
  47. Chengjun Li, Iosef Cristiana, Jia Christina Y H, Han Victor K M, Li Shawn Shun-Cheng: Dual functional roles for the X-linked lymphoproliferative syndrome gene product SAP/SH2D1A in signaling through the signaling lymphocyte activation molecule (SLAM) family of immune receptors. In: J. Biol. Chem.. 278, Nr. 6, United States, Februar 2003, S. 3852–9. doi:10.1074/jbc.M206649200. PMID 12458214.
  48. Betty Chan, Lanyi Arpad, Song Hyun Kyu, Griesbach Jan, Simarro-Grande Maria, Poy Florence, Howie Duncan, Sumegi Janos, Terhorst Cox, Eck Michael J: SAP couples Fyn to SLAM immune receptors. In: Nat. Cell Biol.. 5, Nr. 2, England, Februar 2003, S. 155–60. doi:10.1038/ncb920. PMID 12545174.
  49. A Marie-Cardine, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer S C, Schraven B: Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes. In: J. Biol. Chem.. 272, Nr. 26, UNITED STATES, Juni 1997, S. 16077–80. doi:10.1074/jbc.272.26.16077. PMID 9195899.
  50. Liangtang Wu, Yu Zhenbao, Shen Shi-Hsiang: SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation. In: J. Biol. Chem.. 277, Nr. 43, United States, Oktober 2002, S. 40420–7. doi:10.1074/jbc.M206023200. PMID 12171928.
  51. D A Linseman, Heidenreich K A, Fisher S K: Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway. In: J. Biol. Chem.. 276, Nr. 8, United States, Februar 2001, S. 5622–8. doi:10.1074/jbc.M006812200. PMID 11087735.
  52. Y Iwasaki, Gay B, Wada K, Koizumi S: Association of the Src family tyrosine kinase Fyn with TrkB. In: J. Neurochem.. 71, Nr. 1, UNITED STATES, Juli 1998, S. 106–11. doi:10.1046/j.1471-4159.1998.71010106.x. PMID 9648856.
  53. Chihiro Hisatsune, Kuroda Yukiko, Nakamura Kyoko, Inoue Takafumi, Nakamura Takeshi, Michikawa Takayuki, Mizutani Akihiro, Mikoshiba Katsuhiko: Regulation of TRPC6 channel activity by tyrosine phosphorylation. In: J. Biol. Chem.. 279, Nr. 18, United States, April 2004, S. 18887–94. doi:10.1074/jbc.M311274200. PMID 14761972.
  54. S Uddin, Sher D A, Alsayed Y, Pons S, Colamonici O R, Fish E N, White M F, Platanias L C: Interaction of p59fyn with interferon-activated Jak kinases. In: Biochem. Biophys. Res. Commun.. 235, Nr. 1, UNITED STATES, Juni 1997, S. 83–8. doi:10.1006/bbrc.1997.6741. PMID 9196040.
  55. S Banin, Truong O, Katz D R, Waterfield M D, Brickell P M, Gout I: Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases. In: Curr. Biol.. 6, Nr. 8, ENGLAND, August 1996, S. 981–8. doi:10.1016/S0960-9822(02)00642-5. PMID 8805332.
  56. S Banin, Gout I, Brickell P: Interaction between Wiskott-Aldrich Syndrome protein (WASP) and the Fyn protein-tyrosine kinase. In: Mol. Biol. Rep.. 26, Nr. 3, NETHERLANDS, August 1999, S. 173–7. doi:10.1023/A:1006954206151. PMID 10532312.
  57. O M Rivero-Lezcano, Marcilla A, Sameshima J H, Robbins K C: Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains. In: Mol. Cell. Biol.. 15, Nr. 10, UNITED STATES, Oktober 1995, S. 5725–31. PMID 7565724. Volltext bei PMC: 230823.
  58. E N Neumeister, Zhu Y, Richard S, Terhorst C, Chan A C, Shaw A S: Binding of ZAP-70 to phosphorylated T-cell receptor zeta and eta enhances its autophosphorylation and generates specific binding sites for SH2 domain-containing proteins. In: Mol. Cell. Biol.. 15, Nr. 6, UNITED STATES, Juni 1995, S. 3171–8. PMID 7760813. Volltext bei PMC: 230549.