Biology:FYN

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Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534)[1] is an enzyme that in humans is encoded by the FYN gene.[2]

Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neuronal signaling in development and normal cell physiology. Disruptions in these signaling pathways often have implications in the formation of a variety of cancers. By definition as a proto-oncogene, Fyn codes for proteins that help regulate cell growth. Changes in its DNA sequence transform it into an oncogene that leads to the formation of a different protein with implications for normal cell regulation.[1][3]

Fyn is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist.[4]

History

Fyn is a member of the Src-family of kinases (SFK), the first proto-oncogene to be identified. The discovery of the Src-family in 1976 led to the Nobel prize for medicine in 1989 for J.M Bishop and E.M. Varmus. Fyn was first identified in 1986 as Syn or Slk through probes derived from v-yes and v-fgr. A common feature of SFKs is that they are commonly upregulated in cancers. Fyn is functionally distinct from its family members in that it interacts with FAK and paxillin (PXN) in the regulation of cell morphology and motility.[5]

Function

Fyn is a protein, present in the signaling pathway of integrins, which activates ras. Fyn is a tyrosine-specific phospho-transferase that is a member of the Src family of non-receptor tyrosine protein kinases.[6] (This family also includes Abl, Src, focal adhesion kinase and Janus kinase.) Fyn is located downstream of several cell surface receptors, commonly associated with neuronal development and T-cell signaling. When fyn is activated it causes downstream activation of molecular signals that drive processes crucial to growth and motility of cells.[5] Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane, where it phosphorylates tyrosine residues on key targets involved in a variety of different signaling pathways. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. Fyn also is a tumor suppressor. When this normal biology is compromised, the altered Fyn becomes involved in the neoplastic transformation of normal cells to cancerous ones following the pathway from pre-invasive, to invasive, and ultimately metastasis.[3]

Fyn also appears to play an important role in fertilization including in the rapid Inositol trisphosphate-mediated calcium signaling which occurs when oocyte and sperm interact. Fyn expression levels are much higher in oocytes than even neurons and T-cells and it has been suggested to be an ‘oocyte-specific kinase’.[7] Several studies point to Fyn as being responsible for dramatic biochemical changes in the oocyte cortex during oocyte maturation.[8] Fyn may also play an important role in proper shaping of sperm head and acrosome within the testis and possibly has an additional role in the sperm acrosome reaction.[9]

Role in signaling pathways

An understanding of the role of fyn in normal biology is crucial to the understanding of its role in cancer, as cancer is the dysregulation of these normal pathways. Knowing which pathways involve Fyn will provide key insight for the development of potential pharmacologic agents to attenuate this uncontrolled signaling.

At least three tools have been useful in discerning a requirement for Fyn function in a particular signaling system:

  • cells derived from Fyn-/- mice (as well as cells derived from Fyn, Src, Yes, Fyn triple knockout mice (SYF));
  • a kinase-inactive, dominant negative mutant form of Fyn (K299M);
  • pharmacologic inhibitors of Src family kinases, such as PP2; note that PP2 also inhibits other tyrosine protein kinases such as Abl, PDGFR and c-Kit.

Using these tools, a requirement for Fyn has been shown for the following signaling pathways: T and B cell receptor signaling,[10][11] integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. Fyn also has an important role to play in TLR-mediated immune responses from T cells.[12]

Interactions

FYN has been shown to interact with:


Role in cancer biology

The Src family of kinases is commonly associated with its role in “invasion and tumor progression, epithelial-to-mesenchymal transition, angiogenesis, and development of metastasis,” all hallmarks of cancer progression.[5] Fyn’s normal function in cellular growth and proliferation has the potential to be exploited in the progression and metastasis of cancer cells. Overexpression of Fyn has been found to drive morphologic transformation in normal cells and increase “anchorage-independent growth and prominent morphologic changes.” [1]

Fyn overexpression has been studied in relation to the following cancers: prostate cancer, glioblastoma multiform, squamous cell carcinoma of the head and neck, pancreatic cancer, chronic melogenic leukemia, and melanoma.[1][72] This overexpression triggers a promotion of “anti-apoptotic activity of Akt” in prostate cancer, meaning that these cells have gained the ability to avoid the normal cell death pathways (a common hallmark of cancer).[3] Additionally, in glioblastoma multiform, Src and Fyn have been found to be “effectors of oncogenic EGFR signaling” which has led to tumor invasion and cancer cell survival.[1]

Fyn’s normal role in cell migration and adhesion enables it to utilize the normal cell biology of integrin and FAK for cancer growth. Normal integrin is a cell surface receptor that interacts with the extracellular matrix to send signals influencing cell shape and motility. Normal FAK is a tyrosine kinase that gets recruited to focal adhesion sites and plays a key role in directed cell movement. These normal pathways plan a key role in “mediation of Fyn transmitted cellular events impacting shape and motility.” A compromised version of this pathway would enable cancer cells to change shape and motility, increasing the possibility for advanced invasion and metastasis. Additional pathways under investigation regarding Fyn’s role in cancer progression include: the Rac and Rho family of GTPases, Ras, Erk, and MAPK.[1][3]

Because of this, Fyn has been a common target for anti-cancer therapeutic research. The inhibition of Fyn (like other SFKs) results in decreased cell growth. Furthermore, “expression of kinase-dead-Fyn (KD-Fyn), a specific competitor of endogenous Fyn,” was found to reduce the size of primary tumors in mice. Specifically targeting the unique identifying properties of Fyn as well as inhibiting FAK and PXN has the potential to create a very effective molecularly targeted combination cancer therapy.[3][5] Fyn inhibitors are also being explored as potential therapies for Alzheimer's Disease.[73]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Saito, Yoshihito D.; Jensen, Ana R.; Salgia, Ravi; Posadas, Edwin M. (2010-04-01). "Fyn" (in en). Cancer 116 (7): 1629–1637. doi:10.1002/cncr.24879. ISSN 1097-0142. PMID 20151426. 
  2. ↑ "yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family". Proceedings of the National Academy of Sciences of the United States of America 83 (15): 5459–63. August 1986. doi:10.1073/pnas.83.15.5459. PMID 3526330. Bibcode: 1986PNAS...83.5459S. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Posadas, Edwin M.; Al-Ahmadie, Hikmat; Robinson, Victoria L.; Jagadeeswaran, Ramasamy; Otto, Kristen; Kasza, Kristen E.; Tretiakov, Maria; Siddiqui, Javed et al. (2009-01-01). "FYN is overexpressed in human prostate cancer" (in en). BJU International 103 (2): 171–177. doi:10.1111/j.1464-410X.2008.08009.x. ISSN 1464-410X. PMID 18990162. 
  4. ↑ "Entrez Gene: FYN FYN oncogene related to SRC, FGR, YES". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2534. 
  5. ↑ 5.0 5.1 5.2 5.3 Sen, Banibrata; Johnson, Faye M. (2011-04-04). "Regulation of Src Family Kinases in Human Cancers" (in en). Journal of Signal Transduction 2011: 865819. doi:10.1155/2011/865819. ISSN 2090-1739. PMID 21776389. 
  6. ↑ "Fyn, a Src family tyrosine kinase". The International Journal of Biochemistry & Cell Biology 30 (11): 1159–62. November 1998. doi:10.1016/S1357-2725(98)00089-2. PMID 9839441. 
  7. ↑ Kinsey, William H. (May 24, 2014). "SRC-Family Tyrosine Kinases in Oogenesis, Oocyte Maturation and Fertilization: An Evolutionary Perspective". in Sutovsky, P. Posttranslational Protein Modifications in the Reproductive System. Advances in Experimental Medicine and Biology. 759. Springer. pp. 100–110. doi:10.1007/978-1-4939-0817-2_3. ISBN 978-1-4939-0816-5. 
  8. ↑ McGinnis, Lynda K.; Limback, S. Darlene; Albertini, David F. (Jan 1, 2013). "Chapter Eight - Signaling Modalities During Oogenesis in Mammals". in Wassarman, Paul M.. Current Topics in Developmental Biology. 102. Academic Press. pp. 227–42. doi:10.1016/B978-0-12-416024-8.00008-8. ISBN 9780124160248. 
  9. ↑ Luo, Jinping; Gupta, Vijayalaxmi; Kern, Brian; Tash, Joseph S.; Sanchez, Gladis; Blanco, Gustavo; Kinsey, William H. (January 2012). "Role of FYN Kinase in Spermatogenesis: Defects Characteristic of Fyn-Null Sperm in Mice". Biology of Reproduction 86 (1): 1–8. doi:10.1095/biolreprod.111.093864. PMID 21918125. 
  10. ↑ "The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation". Immunological Reviews 191 (1): 107–18. February 2003. doi:10.1034/j.1600-065X.2003.00015.x. PMID 12614355. 
  11. ↑ "Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation". Oncogene 23 (48): 7990–8000. October 2004. doi:10.1038/sj.onc.1208074. PMID 15489916. 
  12. ↑ "Src kinases central to T-cell receptor signaling regulate TLR-activated innate immune responses from human T cells". Innate Immunity 22 (3): 238–244. April 2016. doi:10.1177/1753425916632305. PMID 26888964. 
  13. ↑ "Interaction of the SH2 domain of Fyn with a cytoskeletal protein, beta-adducin". J. Biol. Chem. 276 (45): 42233–40. November 2001. doi:10.1074/jbc.M102699200. PMID 11526103. 
  14. ↑ "Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells". Exp. Cell Res. 256 (1): 168–78. April 2000. doi:10.1006/excr.2000.4822. PMID 10739664. 
  15. ↑ "Regulation of integrin-mediated p130(Cas) tyrosine phosphorylation in human B cells. A role for p59(Fyn) and SHP2". J. Biol. Chem. 272 (25): 15636–41. June 1997. doi:10.1074/jbc.272.25.15636. PMID 9188452. 
  16. ↑ "Raf-1 interacts with Fyn and Src in a non-phosphotyrosine-dependent manner". J. Biol. Chem. 269 (26): 17749–55. July 1994. doi:10.1016/S0021-9258(17)32504-8. PMID 7517401. 
  17. ↑ "Molecular cloning and characterization of a novel cbl-family gene, cbl-c". Gene 239 (1): 145–54. October 1999. doi:10.1016/s0378-1119(99)00356-x. PMID 10571044. 
  18. ↑ "Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets". Proc. Natl. Acad. Sci. U.S.A. 88 (17): 7844–8. September 1991. doi:10.1073/pnas.88.17.7844. PMID 1715582. Bibcode: 1991PNAS...88.7844H. 
  19. ↑ "Src-related protein tyrosine kinases are physically associated with the surface antigen CD36 in human dermal microvascular endothelial cells". FEBS Lett. 351 (1): 41–4. August 1994. doi:10.1016/0014-5793(94)00814-0. PMID 7521304. 
  20. ↑ "CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes". Blood 91 (10): 3901–8. May 1998. doi:10.1182/blood.V91.10.3901. PMID 9573028. 
  21. ↑ 21.0 21.1 "p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction". Mol. Cell. Biol. 23 (7): 2287–97. April 2003. doi:10.1128/mcb.23.7.2287-2297.2003. PMID 12640114. 
  22. ↑ "alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity". J. Biol. Chem. 276 (17): 13541–6. April 2001. doi:10.1074/jbc.M008035200. PMID 11278378. 
  23. ↑ "Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho". J. Cell Biol. 162 (1): 99–111. July 2003. doi:10.1083/jcb.200211025. PMID 12835311. 
  24. ↑ "c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination". J. Immunol. 169 (7): 3793–800. October 2002. doi:10.4049/jimmunol.169.7.3793. PMID 12244174. 
  25. ↑ 25.0 25.1 "Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases". J. Biol. Chem. 273 (15): 8867–74. April 1998. doi:10.1074/jbc.273.15.8867. PMID 9535867. 
  26. ↑ "Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor". EMBO J. 12 (3): 943–50. March 1993. doi:10.1002/j.1460-2075.1993.tb05735.x. PMID 7681396. 
  27. ↑ 27.0 27.1 "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A". Proc. Natl. Acad. Sci. U.S.A. 96 (2): 435–40. January 1999. doi:10.1073/pnas.96.2.435. PMID 9892651. Bibcode: 1999PNAS...96..435T. 
  28. ↑ 28.0 28.1 "Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia". Brain Res. 955 (1–2): 123–32. November 2002. doi:10.1016/s0006-8993(02)03376-0. PMID 12419528. 
  29. ↑ "Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins". Biochemistry 40 (48): 14585–92. December 2001. doi:10.1021/bi011247r. PMID 11724572. 
  30. ↑ "Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity". Oncogene 18 (39): 5413–22. September 1999. doi:10.1038/sj.onc.1202917. PMID 10498895. 
  31. ↑ "T cell receptor zeta/CD3-p59fyn(T)-associated p120/130 binds to the SH2 domain of p59fyn(T)". J. Exp. Med. 178 (6): 2107–13. December 1993. doi:10.1084/jem.178.6.2107. PMID 7504057. 
  32. ↑ 32.0 32.1 "Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130". J. Biol. Chem. 273 (40): 25789–95. October 1998. doi:10.1074/jbc.273.40.25789. PMID 9748251. 
  33. ↑ "Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor". FEBS Lett. 509 (2): 255–62. December 2001. doi:10.1016/s0014-5793(01)03174-x. PMID 11741599. 
  34. ↑ "Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain". FEBS Lett. 373 (3): 265–8. October 1995. doi:10.1016/0014-5793(95)01051-f. PMID 7589480. 
  35. ↑ "Pituitary adenylate cyclase-activating polypeptide (PACAP(1-38)) enhances N-methyl-D-aspartate receptor function and brain-derived neurotrophic factor expression via RACK1". J. Biol. Chem. 278 (11): 9630–8. March 2003. doi:10.1074/jbc.M209141200. PMID 12524444. 
  36. ↑ "NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5710–5. April 2002. doi:10.1073/pnas.062046299. PMID 11943848. Bibcode: 2002PNAS...99.5710Y. 
  37. ↑ "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". Neurosci. Lett. 348 (3): 185–9. September 2003. doi:10.1016/s0304-3940(03)00784-5. PMID 12932824. 
  38. ↑ "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". J. Cereb. Blood Flow Metab. 19 (8): 880–8. August 1999. doi:10.1097/00004647-199908000-00007. PMID 10458595. 
  39. ↑ "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. 275 (3): 2219–30. January 2000. doi:10.1074/jbc.275.3.2219. PMID 10636929. 
  40. ↑ "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. 271 (41): 25646–56. October 1996. doi:10.1074/jbc.271.41.25646. PMID 8810341. 
  41. ↑ "A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn". J. Biol. Chem. 274 (46): 33131–42. November 1999. doi:10.1074/jbc.274.46.33131. PMID 10551884. 
  42. ↑ "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene 21 (13): 2037–50. March 2002. doi:10.1038/sj.onc.1205271. PMID 11960376. 
  43. ↑ "Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling". J. Biol. Chem. 272 (10): 6214–9. March 1997. doi:10.1074/jbc.272.10.6214. PMID 9045636. 
  44. ↑ "Lck-dependent Fyn activation requires C terminus-dependent targeting of kinase-active Lck to lipid rafts". The Journal of Biological Chemistry 283 (39): 26409–22. 2008. doi:10.1074/jbc.M710372200. PMID 18660530. 
  45. ↑ "Disruption of Fyn SH3 domain interaction with a proline-rich motif in liver kinase B1 results in activation of AMP-activated protein kinase". PLOS ONE 9 (2): e89604. 2014. doi:10.1371/journal.pone.0089604. PMID 24586906. Bibcode: 2014PLoSO...989604Y. 
  46. ↑ "Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases". Kidney Int. 64 (2): 404–13. August 2003. doi:10.1046/j.1523-1755.2003.00097.x. PMID 12846735. 
  47. ↑ "Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin". J. Biol. Chem. 278 (23): 20716–23. June 2003. doi:10.1074/jbc.M301689200. PMID 12668668. 
  48. ↑ "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". J. Exp. Med. 191 (9): 1591–604. May 2000. doi:10.1084/jem.191.9.1591. PMID 10790433. 
  49. ↑ "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". Biochem. J.. 288 288 (2): 395–405. December 1992. doi:10.1042/bj2880395. PMID 1334406. 
  50. ↑ "Direct interaction in T-cells between thetaPKC and the tyrosine kinase p59fyn". J. Biol. Chem. 274 (27): 19003–10. July 1999. doi:10.1074/jbc.274.27.19003. PMID 10383400. 
  51. ↑ "RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes". J. Exp. Med. 185 (6): 1055–63. March 1997. doi:10.1084/jem.185.6.1055. PMID 9091579. 
  52. ↑ "Protein-tyrosine kinase Pyk2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402". J. Biol. Chem. 275 (26): 19645–52. June 2000. doi:10.1074/jbc.M909828199. PMID 10867021. 
  53. ↑ "Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling". J. Exp. Med. 185 (7): 1253–9. April 1997. doi:10.1084/jem.185.7.1253. PMID 9104812. 
  54. ↑ "Specific interactions of neuronal focal adhesion kinase isoforms with Src kinases and amphiphysin". J. Neurochem. 84 (2): 253–65. January 2003. doi:10.1046/j.1471-4159.2003.01519.x. PMID 12558988. 
  55. ↑ "The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases". J. Biol. Chem. 276 (20): 17199–205. May 2001. doi:10.1074/jbc.M011185200. PMID 11278857. 
  56. ↑ "Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn". EMBO J. 28 (22): 3564–78. 2009. doi:10.1038/emboj.2009.289. PMID 19816407. 
  57. ↑ "Unc119, a novel activator of Lck/Fyn, is essential for T cell activation". J. Exp. Med. 199 (3): 369–79. February 2004. doi:10.1084/jem.20030589. PMID 14757743. 
  58. ↑ "p250GAP, a neural RhoGAP protein, is associated with and phosphorylated by Fyn". Biochem. Biophys. Res. Commun. 306 (1): 151–5. June 2003. doi:10.1016/s0006-291x(03)00923-9. PMID 12788081. 
  59. ↑ "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". J. Biol. Chem. 278 (6): 3852–9. February 2003. doi:10.1074/jbc.M206649200. PMID 12458214. 
  60. ↑ "SAP couples Fyn to SLAM immune receptors". Nat. Cell Biol. 5 (2): 155–60. February 2003. doi:10.1038/ncb920. PMID 12545174. 
  61. ↑ "Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes". J. Biol. Chem. 272 (26): 16077–80. June 1997. doi:10.1074/jbc.272.26.16077. PMID 9195899. 
  62. ↑ "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation". J. Biol. Chem. 277 (43): 40420–7. October 2002. doi:10.1074/jbc.M206023200. PMID 12171928. 
  63. ↑ "Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway". J. Biol. Chem. 276 (8): 5622–8. February 2001. doi:10.1074/jbc.M006812200. PMID 11087735. 
  64. ↑ "Regulation of TRPC6 channel activity by tyrosine phosphorylation". J. Biol. Chem. 279 (18): 18887–94. April 2004. doi:10.1074/jbc.M311274200. PMID 14761972. 
  65. ↑ 65.0 65.1 "Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau". J. Neurosci. 22 (3): 698–707. February 2002. doi:10.1523/JNEUROSCI.22-03-00698.2002. PMID 11826099. 
  66. ↑ "Association of the Src family tyrosine kinase Fyn with TrkB". J. Neurochem. 71 (1): 106–11. July 1998. doi:10.1046/j.1471-4159.1998.71010106.x. PMID 9648856. 
  67. ↑ "Interaction of p59fyn with interferon-activated Jak kinases". Biochem. Biophys. Res. Commun. 235 (1): 83–8. June 1997. doi:10.1006/bbrc.1997.6741. PMID 9196040. 
  68. ↑ "Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases". Curr. Biol. 6 (8): 981–8. August 1996. doi:10.1016/s0960-9822(02)00642-5. PMID 8805332. 
  69. ↑ "Interaction between Wiskott-Aldrich Syndrome protein (WASP) and the Fyn protein-tyrosine kinase". Mol. Biol. Rep. 26 (3): 173–7. August 1999. doi:10.1023/A:1006954206151. PMID 10532312. 
  70. ↑ "Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains". Mol. Cell. Biol. 15 (10): 5725–31. October 1995. doi:10.1128/MCB.15.10.5725. PMID 7565724. 
  71. ↑ "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". Mol. Cell. Biol. 15 (6): 3171–8. June 1995. doi:10.1128/mcb.15.6.3171. PMID 7760813. 
  72. ↑ Yadav, Vipin; Denning, Mitchell F. (2011-05-01). "Fyn is induced by Ras/PI3K/Akt signaling and is required for enhanced invasion/migration" (in en). Molecular Carcinogenesis 50 (5): 346–352. doi:10.1002/mc.20716. ISSN 1098-2744. PMID 21480388. 
  73. ↑ "A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease". Alzheimer's Research & Therapy 7 (1): 35. 2015. doi:10.1186/s13195-015-0119-0. PMID 25874001. 

Further reading

External links

  • Overview of all the structural information available in the PDB for UniProt: P06241 (Human Tyrosine-protein kinase Fyn) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: P39688 (Mouse Tyrosine-protein kinase Fyn) at the PDBe-KB.



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