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词条 LYN
释义

  1. Function

  2. Pathology

  3. Interactions

  4. See also

  5. References

  6. Further reading

{{other uses|Lyn (disambiguation)}}{{Infobox_gene}}Tyrosine-protein kinase Lyn is a protein that in humans is encoded in humans by the LYN gene.[1]

Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells,[2] in neural tissues[3] liver, and adipose tissue.[4] In various hematopoietic cells, Lyn has emerged as a key enzyme involved in the regulation of cell activation. In these cells, a small amount of LYN is associated with cell surface receptor proteins, including the B cell antigen receptor (BCR),[5][6] CD40,[7] or CD19.[8] The abbreviation Lyn is derived from Lck/Yes novel tyrosine kinase, Lck and Yes also being members of the Src kinase family.

Function

Lyn has been described to have an inhibitory role in myeloid lineage proliferation.[9] Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation. LYN activation triggers a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phosholipase Cγ2 (PLCγ2) and phosphatidyl inositol-3 kinase.[8][10] These kinases provide activation signals, which play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FCγRIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1,[11][12][13][14][15] which further downmodulate signaling pathways, attenuate cell activation and can mediate tolerance. In B cells, Lyn sets the threshold of cell signaling and maintains the balance between activation and inhibition. Lyn thus functions as a rheostat that modulates signaling rather than as a binary on-off switch.[16][17][18]

Lyn has also been implicated to have a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1). This phosphorylation of IRS1 leads to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization.[19] In turn, activation of the insulin receptor has been shown to increase autophosphorylation of Lyn suggesting a possible feedback loop.[20]

The insulin secretagogue, glimepiride (Amaryl®) activates Lyn in adipocytes via the disruption of lipid rafts.[21] This indirect Lyn activation may modulate the extrapancreatic glycemic control activity of glimepiride.[21][22] Tolimidone (MLR-1023) is a small molecule lyn activator that is currently under Phase 2a investigation for Type II diabetes.[23] In June, 2016, the sponsor of these studies, Melior Discovery, announced positive results from their Phase 2a study with tolimidone in diabetic patients[24], and the continuation of additional clinical studies[25].

Lyn has been shown to protect against hepatcellular apoptosis and promote liver regeneration through the preservation of hepatocellular mitochondrial integrity.[26]

Pathology

Much of the current knowledge about Lyn has emerged from studies of genetically manipulated mice. Lyn deficient mice display a phenotype that includes splenomegaly, a dramatic increase in numbers of myeloid progenitors and monocyte/macrophage tumors. Biochemical analysis of cells from these mutants revealed that Lyn is essential in establishing ITIM-dependent inhibitory signaling and for activation of specific protein tyrosine phosphatases within myeloid cells.[9]

Mice that expressed a hyperactive Lyn allele were tumor free and displayed no propensity toward hematological malignancy. These mice have reduced numbers of conventional B lymphocytes, down-regulated surface immunoglobulin M and costimulatory molecules, and elevated numbers of B1a B cells. With age these animals developed a glomerulonephritis phenotype associated with a 30% reduction in life expectancy.[27]

Interactions

LYN has been shown to interact with:

c-Kit,[28]

{{div col|colwidth=20em}}
  • BCAR1,[29][30]
  • CD117,[31][32]
  • CD22,[33][34]
  • Cdk1,[35][36]
  • DOK1,[31][37]
  • EPOR[38]
  • GPVI,[39]
  • INPP5D,[40]
  • IRS1,[41]
  • LCP2,[42]
  • MUC1,[43]
  • NEDD9,[29]
  • PLCG2,[44][45]
  • PPP1R15A,[46]
  • PTPRC,[47]
  • Syk,[48]
  • TRPV4,[49] and
  • UNC119.[50]
{{Div col end}}

See also

  • Lyn-CD22-SHP-1 pathway

References

1. ^{{cite journal | vauthors = Yamanashi Y, Fukushige S, Semba K, Sukegawa J, Miyajima N, Matsubara K, Yamamoto T, Toyoshima K | title = The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck | journal = Molecular and Cellular Biology | volume = 7 | issue = 1 | pages = 237–43 | date = Jan 1987 | pmid = 3561390 | pmc = 365062 | doi = 10.1128/MCB.7.1.237}}
2. ^{{cite journal | vauthors = Yamanashi Y, Mori S, Yoshida M, Kishimoto T, Inoue K, Yamamoto T, Toyoshima K | title = Selective expression of a protein-tyrosine kinase, p56lyn, in hematopoietic cells and association with production of human T-cell lymphotropic virus type I | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 17 | pages = 6538–42 | date = Sep 1989 | pmid = 2505253 | pmc = 297879 | doi = 10.1073/pnas.86.17.6538 }}
3. ^{{cite journal | vauthors = Umemori H, Wanaka A, Kato H, Takeuchi M, Tohyama M, Yamamoto T | title = Specific expressions of Fyn and Lyn, lymphocyte antigen receptor-associated tyrosine kinases, in the central nervous system | journal = Brain Research. Molecular Brain Research | volume = 16 | issue = 3–4 | pages = 303–10 | date = Dec 1992 | pmid = 1337939 | doi = 10.1016/0169-328X(92)90239-8 }}
4. ^{{cite journal | vauthors = Yamada E, Pessin JE, Kurland IJ, Schwartz GJ, Bastie CC | title = Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine phosphorylation of LKB1 | journal = Cell Metabolism | volume = 11 | issue = 2 | pages = 113–124 | date = Feb 2010 | pmid = 20142099 | pmc = 2830006 | doi = 10.1016/j.cmet.2009.12.010 }}
5. ^{{cite journal | vauthors = Yamamoto T, Yamanashi Y, Toyoshima K | title = Association of Src-family kinase Lyn with B-cell antigen receptor | journal = Immunological Reviews | volume = 132 | issue = | pages = 187–206 | date = Apr 1993 | pmid = 8349296 | doi = 10.1111/j.1600-065X.1993.tb00843.x }}
6. ^{{cite journal | vauthors = Campbell MA, Sefton BM | title = Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases | journal = Molecular and Cellular Biology | volume = 12 | issue = 5 | pages = 2315–21 | date = May 1992 | pmid = 1569953 | pmc = 364403 | doi = 10.1128/MCB.12.5.2315| url = http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=1569953 }}
7. ^{{cite journal | vauthors = Ren CL, Morio T, Fu SM, Geha RS | title = Signal transduction via CD40 involves activation of lyn kinase and phosphatidylinositol-3-kinase, and phosphorylation of phospholipase C gamma 2 | journal = The Journal of Experimental Medicine | volume = 179 | issue = 2 | pages = 673–80 | date = Feb 1994 | pmid = 7507510 | pmc = 2191357 | doi = 10.1084/jem.179.2.673 }}
8. ^1 Campbell 1999
9. ^1 {{cite journal | vauthors = Harder KW, Parsons LM, Armes J, Evans N, Kountouri N, Clark R, Quilici C, Grail D, Hodgson GS, Dunn AR, Hibbs ML | title = Gain- and loss-of-function Lyn mutant mice define a critical inhibitory role for Lyn in the myeloid lineage | journal = Immunity | volume = 15 | issue = 4 | pages = 603–615 | date = Oct 2001 | pmid = 11672542 | doi = 10.1016/S1074-7613(01)00208-4 }}
10. ^{{cite journal | vauthors = Yamanashi Y, Fukui Y, Wongsasant B, Kinoshita Y, Ichimori Y, Toyoshima K, Yamamoto T | title = Activation of Src-like protein-tyrosine kinase Lyn and its association with phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 3 | pages = 1118–22 | date = Feb 1992 | pmid = 1371009 | pmc = 48397 | doi = 10.1073/pnas.89.3.1118 }}
11. ^{{cite journal | vauthors = Cornall RJ, Cyster JG, Hibbs ML, Dunn AR, Otipoby KL, Clark EA, Goodnow CC | title = Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection | journal = Immunity | volume = 8 | issue = 4 | pages = 497–508 | date = Apr 1998 | pmid = 9586639 | doi = 10.1016/S1074-7613(00)80554-3 | url = http://linkinghub.elsevier.com/retrieve/pii/S1074-7613(00)80554-3 }}
12. ^{{cite journal | vauthors = Smith KG, Tarlinton DM, Doody GM, Hibbs ML, Fearon DT | title = Inhibition of the B cell by CD22: a requirement for Lyn | journal = The Journal of Experimental Medicine | volume = 187 | issue = 5 | pages = 807–11 | date = Mar 1998 | pmid = 9480991 | pmc = 2212179 | doi = 10.1084/jem.187.5.807 }}
13. ^{{cite journal | vauthors = Chan VW, Lowell CA, DeFranco AL | title = Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes | journal = Current Biology | volume = 8 | issue = 10 | pages = 545–53 | date = May 1998 | pmid = 9601638 | doi = 10.1016/S0960-9822(98)70223-4 | url = http://linkinghub.elsevier.com/retrieve/pii/S0960-9822(98)70223-4 }}
14. ^{{cite journal | vauthors = Nishizumi H, Horikawa K, Mlinaric-Rascan I, Yamamoto T | title = A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals | journal = The Journal of Experimental Medicine | volume = 187 | issue = 8 | pages = 1343–8 | date = Apr 1998 | pmid = 9547345 | pmc = 2212230 | doi = 10.1084/jem.187.8.1343 }}
15. ^{{cite journal | vauthors = Maeda A, Scharenberg AM, Tsukada S, Bolen JB, Kinet JP, Kurosaki T | title = Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1 | journal = Oncogene | volume = 18 | issue = 14 | pages = 2291–7 | date = Apr 1999 | pmid = 10327049 | doi = 10.1038/sj.onc.1202552 }}
16. ^{{cite journal | vauthors = Lowell CA | title = Src-family kinases: rheostats of immune cell signaling | journal = Molecular Immunology | volume = 41 | issue = 6–7 | pages = 631–43 | date = Jul 2004 | pmid = 15220000 | doi = 10.1016/j.molimm.2004.04.010 }}
17. ^{{cite journal | vauthors = Saijo K, Schmedt C, Su IH, Karasuyama H, Lowell CA, Reth M, Adachi T, Patke A, Santana A, Tarakhovsky A | title = Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development | journal = Nature Immunology | volume = 4 | issue = 3 | pages = 274–9 | date = Mar 2003 | pmid = 12563261 | doi = 10.1038/ni893 }}
18. ^{{cite journal | vauthors = Xu Y, Harder KW, Huntington ND, Hibbs ML, Tarlinton DM | title = Lyn tyrosine kinase: accentuating the positive and the negative | journal = Immunity | volume = 22 | issue = 1 | pages = 9–18 | date = Jan 2005 | pmid = 15664155 | doi = 10.1016/j.immuni.2004.12.004 }}
19. ^{{cite journal | vauthors = Müller G, Wied S, Frick W | title = Cross talk of pp125(FAK) and pp59(Lyn) non-receptor tyrosine kinases to insulin-mimetic signaling in adipocytes | journal = Molecular and Cellular Biology | volume = 20 | issue = 13 | pages = 4708–4723 | date = Jul 2000 | pmid = 10848597 | pmc = 85892 | doi = 10.1128/mcb.20.13.4708-4723.2000 }}
20. ^{{cite journal | vauthors = Anderwald C, Müller G, Koca G, Fürnsinn C, Waldhäusl W, Roden M | title = Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insulin receptor substrate-2 | journal = Molecular Endocrinology | volume = 16 | issue = 7 | pages = 1612–1628 | date = Jul 2002 | pmid = 12089355 | pmc = | doi = 10.1210/me.16.7.1612 }}
21. ^1 {{cite journal | vauthors = Müller G | title = The molecular mechanism of the insulin-mimetic/sensitizing activity of the antidiabetic sulfonylurea drug Amaryl | journal = Molecular Medicine | volume = 6 | issue = 11 | pages = 907–933 | date = Nov 2000 | pmid = 11147570 | pmc = 1949923 | doi = 10.1007/BF03401827}}
22. ^{{cite journal | vauthors = Müller G, Schulz A, Wied S, Frick W | title = Regulation of lipid raft proteins by glimepiride- and insulin-induced glycosylphosphatidylinositol-specific phospholipase C in rat adipocytes | journal = Biochemical Pharmacology | volume = 69 | issue = 5 | pages = 761–780 | date = Mar 2005 | pmid = 15710354 | doi = 10.1016/j.bcp.2004.11.014 }}
23. ^{{cite web|title=Melior Pharmaceuticals Initiates Phase 2 Study with MLR-1023 for Type 2 Diabetes|url=http://www.businesswire.com/news/home/20150303005277/en/Melior-Pharmaceuticals-Initiates-Phase-2-Study-MLR-1023#.VVy7eGCKKkJ|publisher=Business Wire|accessdate=March 3, 2015}}
24. ^{{Cite web|url=http://www.businesswire.com/news/home/20160613005028/en/Melior-Pharmaceuticals-Announces-Positive-Phase-2A-Results|title=Melior Pharmaceuticals Announces Positive Phase 2A Results in Type 2 Diabetes Study|website=www.businesswire.com|language=en|access-date=2017-08-04}}
25. ^{{Cite web|url=http://www.meliordiscovery.com/media_press.html|title=Melior Discovery website press releases|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}
26. ^{{cite journal | vauthors = Gringeri E, Carraro A, Tibaldi E, D'Amico FE, Mancon M, Toninello A, Pagano MA, Vio C, Cillo U, Brunati AM | title = Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration | journal = The Biochemical Journal | volume = 425 | issue = 2 | pages = 401–12 | date = December 2009 | pmid = 19832701 | doi = 10.1042/BJ20090902 }}
27. ^{{cite journal | vauthors = Hibbs ML, Harder KW, Armes J, Kountouri N, Quilici C, Casagranda F, Dunn AR, Tarlinton DM | title = Sustained activation of Lyn tyrosine kinase in vivo leads to autoimmunity | journal = The Journal of Experimental Medicine | volume = 196 | issue = 12 | pages = 1593–604 | date = Dec 2002 | pmid = 12486102 | pmc = 2196073 | doi = 10.1084/jem.20020515 }}
28. ^{{Cite journal|last=Linnekin|first=Diana|last2=DeBerry|first2=Candy S.|last3=Mou|first3=Sherry|date=1997-10-24|title=Lyn Associates with the Juxtamembrane Region of c-Kit and Is Activated by Stem Cell Factor in Hematopoietic Cell Lines and Normal Progenitor Cells|url=http://www.jbc.org/content/272/43/27450|journal=Journal of Biological Chemistry|language=en|volume=272|issue=43|pages=27450–27455|doi=10.1074/jbc.272.43.27450|issn=0021-9258|pmid=9341198}}
29. ^1 {{cite journal | vauthors = Manié SN, Beck AR, Astier A, Law SF, Canty T, Hirai H, Druker BJ, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin JD, Golemis EA, Freedman AS | title = Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells | journal = The Journal of Biological Chemistry | volume = 272 | issue = 7 | pages = 4230–6 | date = Feb 1997 | pmid = 9020138 | doi = 10.1074/jbc.272.7.4230 }}
30. ^{{cite journal | vauthors = Qiu W, Cobb RR, Scholz W | title = Inhibition of p130cas tyrosine phosphorylation by calyculin A | journal = Journal of Leukocyte Biology | volume = 63 | issue = 5 | pages = 631–5 | date = May 1998 | pmid = 9581808 | doi = 10.1002/jlb.63.5.631}}
31. ^1 {{cite journal | vauthors = Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD | title = Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling | journal = The Journal of Biological Chemistry | volume = 277 | issue = 16 | pages = 13732–8 | date = Apr 2002 | pmid = 11825908 | doi = 10.1074/jbc.M200277200 }}
32. ^{{cite journal | vauthors = Linnekin D, DeBerry CS, Mou S | title = Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells | journal = The Journal of Biological Chemistry | volume = 272 | issue = 43 | pages = 27450–5 | date = Oct 1997 | pmid = 9341198 | doi = 10.1074/jbc.272.43.27450 }}
33. ^{{cite journal | vauthors = Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF | title = CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux | journal = The Journal of Biological Chemistry | volume = 275 | issue = 23 | pages = 17420–7 | date = Jun 2000 | pmid = 10748054 | doi = 10.1074/jbc.M001892200 }}
34. ^{{cite journal | vauthors = Greer SF, Justement LB | title = CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1 | journal = Journal of Immunology | volume = 162 | issue = 9 | pages = 5278–86 | date = May 1999 | pmid = 10228003 | doi = }}
35. ^{{cite journal | vauthors = Kharbanda S, Yuan ZM, Rubin E, Weichselbaum R, Kufe D | title = Activation of Src-like p56/p53lyn tyrosine kinase by ionizing radiation | journal = The Journal of Biological Chemistry | volume = 269 | issue = 32 | pages = 20739–43 | date = Aug 1994 | pmid = 8051175 | doi = }}
36. ^{{cite journal | vauthors = Pathan NI, Geahlen RL, Harrison ML | title = The protein-tyrosine kinase Lck associates with and is phosphorylated by Cdc2 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 44 | pages = 27517–23 | date = Nov 1996 | pmid = 8910336 | doi = 10.1074/jbc.271.44.27517 }}
37. ^{{cite journal | vauthors = van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M | title = Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells | journal = Blood | volume = 96 | issue = 10 | pages = 3406–13 | date = Nov 2000 | pmid = 11071635 | doi = }}
38. ^{{cite journal | vauthors = Chin H, Arai A, Wakao H, Kamiyama R, Miyasaka N, Miura O | title = Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway | journal = Blood | volume = 91 | issue = 10 | pages = 3734–45 | date = May 1998 | pmid = 9573010 | doi = }}
39. ^{{cite journal | vauthors = Suzuki-Inoue K, Tulasne D, Shen Y, Bori-Sanz T, Inoue O, Jung SM, Moroi M, Andrews RK, Berndt MC, Watson SP | title = Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling | journal = The Journal of Biological Chemistry | volume = 277 | issue = 24 | pages = 21561–6 | date = Jun 2002 | pmid = 11943772 | doi = 10.1074/jbc.M201012200 }}
40. ^{{cite journal | vauthors = Baran CP, Tridandapani S, Helgason CD, Humphries RK, Krystal G, Marsh CB | title = The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 40 | pages = 38628–36 | date = Oct 2003 | pmid = 12882960 | doi = 10.1074/jbc.M305021200 }}
41. ^{{cite journal | vauthors = Müller G, Wied S, Frick W | title = Cross talk of pp125(FAK) and pp59(Lyn) non-receptor tyrosine kinases to insulin-mimetic signaling in adipocytes | journal = Molecular and Cellular Biology | volume = 20 | issue = 13 | pages = 4708–23 | date = Jul 2000 | pmid = 10848597 | pmc = 85892 | doi = 10.1128/mcb.20.13.4708-4723.2000 }}
42. ^{{cite journal | vauthors = Gross BS, Lee JR, Clements JL, Turner M, Tybulewicz VL, Findell PR, Koretzky GA, Watson SP | title = Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets | journal = The Journal of Biological Chemistry | volume = 274 | issue = 9 | pages = 5963–71 | date = Feb 1999 | pmid = 10026222 | doi = 10.1074/jbc.274.9.5963 }}
43. ^{{cite journal | vauthors = Durum SK, Aiello FB | title = Interleukin-7 induces MUC1 | journal = Cancer Biology & Therapy | volume = 2 | issue = 2 | pages = 194–5 | year = 2003 | pmid = 12750562 | doi = 10.4161/cbt.2.2.351 }}
44. ^{{cite journal | vauthors = Pleiman CM, Clark MR, Gauen LK, Winitz S, Coggeshall KM, Johnson GL, Shaw AS, Cambier JC | title = Mapping of sites on the Src family protein tyrosine kinases p55blk, p59fyn, and p56lyn which interact with the effector molecules phospholipase C-gamma 2, microtubule-associated protein kinase, GTPase-activating protein, and phosphatidylinositol 3-kinase | journal = Molecular and Cellular Biology | volume = 13 | issue = 9 | pages = 5877–87 | date = Sep 1993 | pmid = 8395016 | pmc = 360336 | doi = 10.1128/MCB.13.9.5877}}
45. ^{{cite journal | vauthors = Guo B, Kato RM, Garcia-Lloret M, Wahl MI, Rawlings DJ | title = Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex | journal = Immunity | volume = 13 | issue = 2 | pages = 243–53 | date = Aug 2000 | pmid = 10981967 | doi = 10.1016/s1074-7613(00)00024-8 }}
46. ^{{cite journal | vauthors = Grishin AV, Azhipa O, Semenov I, Corey SJ | title = Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 18 | pages = 10172–7 | date = Aug 2001 | pmid = 11517336 | pmc = 56934 | doi = 10.1073/pnas.191130798 }}
47. ^{{cite journal | vauthors = Brown VK, Ogle EW, Burkhardt AL, Rowley RB, Bolen JB, Justement LB | title = Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 25 | pages = 17238–44 | date = Jun 1994 | pmid = 7516335 | doi = }}
48. ^{{cite journal | vauthors = Sidorenko SP, Law CL, Chandran KA, Clark EA | title = Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 2 | pages = 359–63 | date = Jan 1995 | pmid = 7831290 | pmc = 42739 | doi = 10.1073/pnas.92.2.359 }}
49. ^{{cite journal | vauthors = Xu H, Zhao H, Tian W, Yoshida K, Roullet JB, Cohen DM | title = Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress | journal = The Journal of Biological Chemistry | volume = 278 | issue = 13 | pages = 11520–7 | date = Mar 2003 | pmid = 12538589 | doi = 10.1074/jbc.M211061200 }}
50. ^{{cite journal | vauthors = Cen O, Gorska MM, Stafford SJ, Sur S, Alam R | title = Identification of UNC119 as a novel activator of SRC-type tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 278 | issue = 10 | pages = 8837–45 | date = Mar 2003 | pmid = 12496276 | doi = 10.1074/jbc.M208261200 }}

Further reading

{{refbegin|35em}}
  • {{cite journal | vauthors = Jouvin MH, Numerof RP, Kinet JP | title = Signal transduction through the conserved motifs of the high affinity IgE receptor Fc epsilon RI | journal = Seminars in Immunology | volume = 7 | issue = 1 | pages = 29–35 | date = Feb 1995 | pmid = 7612892 | doi = 10.1016/1044-5323(95)90005-5 }}
  • {{cite journal | vauthors = Hibbs ML, Dunn AR | title = Lyn, a src-like tyrosine kinase | journal = The International Journal of Biochemistry & Cell Biology | volume = 29 | issue = 3 | pages = 397–400 | date = Mar 1997 | pmid = 9202419 | doi = 10.1016/S1357-2725(96)00104-5 }}
  • {{cite book | last1= Blasioli |first1=J.|last2= Goodnow |first2=C. C. | title = Lyn/CD22/SHP-1 and Their Importance in Autoimmunity | journal = Current Directions in Autoimmunity | volume = 5 | issue = | pages = 151–60 | year = 2002 | pmid = 11826756 | doi = 10.1159/000060551 | isbn = 978-3-8055-7308-5 }}
  • {{cite journal | vauthors = Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M | title = HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication | journal = Journal of Biosciences | volume = 28 | issue = 3 | pages = 323–35 | date = Apr 2003 | pmid = 12734410 | doi = 10.1007/BF02970151 }}
  • {{cite journal | vauthors = Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M | title = HIV/SIV escape from immune surveillance: focus on Nef | journal = Current HIV Research | volume = 2 | issue = 2 | pages = 141–51 | date = Apr 2004 | pmid = 15078178 | doi = 10.2174/1570162043484924 }}
  • {{cite journal | vauthors = Joseph AM, Kumar M, Mitra D | title = Nef: "necessary and enforcing factor" in HIV infection | journal = Current HIV Research | volume = 3 | issue = 1 | pages = 87–94 | date = Jan 2005 | pmid = 15638726 | doi = 10.2174/1570162052773013 }}
  • {{cite journal | vauthors = Stove V, Verhasselt B | title = Modelling thymic HIV-1 Nef effects | journal = Current HIV Research | volume = 4 | issue = 1 | pages = 57–64 | date = Jan 2006 | pmid = 16454711 | doi = 10.2174/157016206775197583 }}
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