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Gene Review

Lyn  -  Yamaguchi sarcoma viral (v-yes-1) oncogene...

Mus musculus

Synonyms: AA407514, Hck-2, Tyrosine-protein kinase Lyn, V-yes-1 Yamaguchi sarcoma viral related oncogene homolog, p53Lyn, ...
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Disease relevance of Lyn

  • Remarkably, CD19 deficiency suppressed the hyper-responsive phenotype of Lyn(-/-) B cells and autoimmunity characterized by serum autoantibodies and immune complex-mediated glomerulonephritis in Lyn(-/-) mice [1].
  • This study also suggests that reduced activity of Lyn, a negative regulator of mast cell activation, underlies the susceptibility of ASK mice to anaphylaxis and implies that dysregulation of Lyn and other Src family kinases contributes to epileptogenesis [2].
  • BCR signals are down-regulated by Lyn, which phosphorylates inhibitory receptors. lyn(-/-) mice have reduced BCR signaling thresholds and develop autoantibodies, glomerulonephritis, splenomegaly due to myeloid hyperplasia, and increased B-1 cell numbers [3].
  • In vivo infection of Lyn deficient animals also results in a massive splenomegaly characteristic of the virus [4].
  • However, we observe differences in the pathogenesis of Friend erythroleukemia in Lyn-/- mice [4].
  • Together, our findings suggest that Lyn may be a critical kinase mediating nerve injury-induced P2X(4)R upregulation and neuropathic pain [5].

Psychiatry related information on Lyn


High impact information on Lyn

  • Data from knockout experiments in cell lines and mice have revealed distinct functions for the intracellular protein tyrosine kinases (Lyn, Syk, Btk) in BCR signaling and B cell development [7].
  • Mice homozygous for a disruption at the Lyn locus display abnormalities associated with the B lymphocyte lineage and in mast cell function [8].
  • Lyn-/- mice have circulating autoreactive antibodies, and many show severe glomerulonephritis caused by the deposition of IgG immune complexes in the kidney, a pathology reminiscent of systemic lupus erythematosus [8].
  • Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease [8].
  • In these cells, activation of the tyrosine kinase Lyn, an important anti-apoptotic event, was prevented as a consequence of death-receptor stimulation, most likely through association of the receptor with activated SHP-1 [9].

Chemical compound and disease context of Lyn


Biological context of Lyn


Anatomical context of Lyn


Associations of Lyn with chemical compounds


Physical interactions of Lyn

  • We could previously show that, through the Tec-homology domain, Tec is bound to Lyn kinase both in vitro and in vivo [22].
  • Our proposed docking models of the NS-187/Abl complex support the notion that NS-187 is more specific for Lyn than for Src [23].
  • The Lyn SH2 binding profile resembled that of Blk, but differences in the binding specificities of these kinases were also observed [24].
  • HS1 interacts with Lyn and is critical for erythropoietin-induced differentiation of erythroid cells [25].
  • Constitutive CD19/Lyn/Vav complex signaling may therefore be responsible for the establishment of baseline signaling thresholds in B cells before Ag receptor ligation, in addition to accelerating signaling following BCR engagement or other transmembrane signals [26].

Enzymatic interactions of Lyn

  • In addition, Lyn was demonstrated to phosphorylate the EpoR and Stat5 on tyrosines in vitro [14].
  • Here we demonstrate that Lyn can phosphorylate tyrosine residues of the Tec protein, and thereby activate Tec in 3T3 fibroblasts [22].
  • Immunoprecipitation experiments revealed that gamma-tubulin from activated cells formed complexes with Fyn and Syk protein tyrosine kinases and several tyrosine phosphorylated proteins from both wild-type and Lyn(-/-) BMMCs [27].
  • The biochemical basis of this complex trait involves a pathway requiring Lyn to phosphorylate CD22 and recruit SHP-1 to the CD22/BCR complex [28].

Regulatory relationships of Lyn

  • Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors [29].
  • Because Tec is coexpressed with Lyn in many hematopoietic cell types, it has been intriguing to investigate the biological role of the Tec-Lyn association [22].
  • Lyn promoted phosphorylation of c-Kit and association of c-Kit and Dok-1 [30].
  • When wild type Btk is activated by coexpression with Lyn, the tyrosine phosphorylated pool of Btk is highly enriched in the membrane fraction [31].
  • Fast protein liquid chromatography Mono Q column-fractionated MAPK maintains the ability to bind bacterially expressed Lyn, suggesting that the two kinases may interact directly [32].

Other interactions of Lyn

  • 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 [13].
  • A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5 [13].
  • Effects of Lyn, PTEN, or p85alpha haploinsufficiency were observed [12].
  • In the present study, we demonstrate that Lyn, a Src family tyrosine kinase, physically associates with the EpoR in Epo-dependent hematopoietic cell lines, 32D/EpoR-Wt and F36E [14].
  • Similarly, proliferation is increased after introducing a dominant-negative form of Lyn into BaF3/Mpl cells [29].
  • Analysis of lyn(-/-)hck(-/-), lyn(-/-)FcepsilonRIbeta(-/-), and hck(-/-)FcepsilonRIbeta(-/-) cells shows that Hck exerts these functions via both Lyn-dependent and Lyn-independent mechanisms [33].

Analytical, diagnostic and therapeutic context of Lyn

  • Far-Western blotting and synthetic phosphopeptide competition assays further indicated that the Lyn SH2 domain directly binds to the tyrosine-phosphorylated EpoR, most likely through its interaction with phosphorylated Y-464 or Y-479 in the carboxy-terminal region of the EpoR [14].
  • On the basis of immunoprecipitation and sequence analysis data, we propose that the human G-CSFR forms a three-component signaling complex with Lyn and Syk [34].
  • Microarray analysis of Lyn-deficient B cells reveals germinal center-associated nuclear protein and other genes associated with the lymphoid germinal center [35].
  • The presence of Lyn enhanced PU.1 expression in a Northern blot [35].
  • Complementary DNA array analysis of Lyn-deficient DT40 cells shows that the absence of Lyn leads to down-regulation of numerous genes encoding proteins involved in B cell receptor signaling, proliferation, control of transcription, immunity/inflammation response, and cytoskeletal organization [35].


  1. A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice. Hasegawa, M., Fujimoto, M., Poe, J.C., Steeber, D.A., Lowell, C.A., Tedder, T.F. J. Immunol. (2001) [Pubmed]
  2. Dysregulation of Src Family Kinases in Mast Cells from Epilepsy-Resistant ASK versus Epilepsy-Prone EL Mice. Kitaura, J., Kawakami, Y., Maeda-Yamamoto, M., Horejsi, V., Kawakami, T. J. Immunol. (2007) [Pubmed]
  3. Reduced dosage of Bruton's tyrosine kinase uncouples B cell hyperresponsiveness from autoimmunity in lyn-/- mice. Whyburn, L.R., Halcomb, K.E., Contreras, C.M., Lowell, C.A., Witte, O.N., Satterthwaite, A.B. J. Immunol. (2003) [Pubmed]
  4. Mutation of the Lyn tyrosine kinase delays the progression of Friend virus induced erythroleukemia without affecting susceptibility. Subramanian, A., Hegde, S., Correll, P.H., Paulson, R.F. Leuk. Res. (2006) [Pubmed]
  5. Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Tsuda, M., Tozaki-Saitoh, H., Masuda, T., Toyomitsu, E., Tezuka, T., Yamamoto, T., Inoue, K. Glia (2008) [Pubmed]
  6. The activation and subsequent regulatory roles of Lyn and CD19 after B cell receptor ligation are independent. Xu, Y., Beavitt, S.J., Harder, K.W., Hibbs, M.L., Tarlinton, D.M. J. Immunol. (2002) [Pubmed]
  7. Genetic analysis of B cell antigen receptor signaling. Kurosaki, T. Annu. Rev. Immunol. (1999) [Pubmed]
  8. Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Hibbs, M.L., Tarlinton, D.M., Armes, J., Grail, D., Hodgson, G., Maglitto, R., Stacker, S.A., Dunn, A.R. Cell (1995) [Pubmed]
  9. Death receptors bind SHP-1 and block cytokine-induced anti-apoptotic signaling in neutrophils. Daigle, I., Yousefi, S., Colonna, M., Green, D.R., Simon, H.U. Nat. Med. (2002) [Pubmed]
  10. Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice. Nishizumi, H., Taniuchi, I., Yamanashi, Y., Kitamura, D., Ilic, D., Mori, S., Watanabe, T., Yamamoto, T. Immunity (1995) [Pubmed]
  11. Phosphorylation of two regulatory tyrosine residues in the activation of Bruton's tyrosine kinase via alternative receptors. Wahl, M.I., Fluckiger, A.C., Kato, R.M., Park, H., Witte, O.N., Rawlings, D.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  12. 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]
  13. 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]
  14. Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway. Chin, H., Arai, A., Wakao, H., Kamiyama, R., Miyasaka, N., Miura, O. Blood (1998) [Pubmed]
  15. Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn. Fitzer-Attas, C.J., Lowry, M., Crowley, M.T., Finn, A.J., Meng, F., DeFranco, A.L., Lowell, C.A. J. Exp. Med. (2000) [Pubmed]
  16. Positive and negative regulation of mast cell activation by Lyn via the FcepsilonRI. Xiao, W., Nishimoto, H., Hong, H., Kitaura, J., Nunomura, S., Maeda-Yamamoto, M., Kawakami, Y., Lowell, C.A., Ra, C., Kawakami, T. J. Immunol. (2005) [Pubmed]
  17. Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation. Stafford, S., Lowell, C., Sur, S., Alam, R. J. Immunol. (2002) [Pubmed]
  18. Lyn and Syk kinases are sequentially engaged in phagocytosis mediated by Fc gamma R. Strzelecka-Kiliszek, A., Kwiatkowska, K., Sobota, A. J. Immunol. (2002) [Pubmed]
  19. Interactions of Lyn with the antigen receptor during B cell activation. Burg, D.L., Furlong, M.T., Harrison, M.L., Geahlen, R.L. J. Biol. Chem. (1994) [Pubmed]
  20. Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. Hernandez-Hansen, V., Smith, A.J., Surviladze, Z., Chigaev, A., Mazel, T., Kalesnikoff, J., Lowell, C.A., Krystal, G., Sklar, L.A., Wilson, B.S., Oliver, J.M. J. Immunol. (2004) [Pubmed]
  21. Integrin-associated Lyn kinase promotes cell survival by suppressing acid sphingomyelinase activity. Chudakova, D.A., Zeidan, Y.H., Wheeler, B.W., Yu, J., Novgorodov, S.A., Kindy, M.S., Hannun, Y.A., Gudz, T.I. J. Biol. Chem. (2008) [Pubmed]
  22. Tec protein-tyrosine kinase is an effector molecule of Lyn protein-tyrosine kinase. Mano, H., Yamashita, Y., Miyazato, A., Miura, Y., Ozawa, K. FASEB J. (1996) [Pubmed]
  23. Development of NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor. Kimura, S., Niwa, T., Hirabayashi, K., Maekawa, T. Cancer Chemother. Pharmacol. (2006) [Pubmed]
  24. SH2 domains of the protein-tyrosine kinases Blk, Lyn, and Fyn(T) bind distinct sets of phosphoproteins from B lymphocytes. Malek, S.N., Desiderio, S. J. Biol. Chem. (1993) [Pubmed]
  25. HS1 interacts with Lyn and is critical for erythropoietin-induced differentiation of erythroid cells. Ingley, E., Sarna, M.K., Beaumont, J.G., Tilbrook, P.A., Tsai, S., Takemoto, Y., Williams, J.H., Klinken, S.P. J. Biol. Chem. (2000) [Pubmed]
  26. CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation. Fujimoto, M., Poe, J.C., Jansen, P.J., Sato, S., Tedder, T.F. J. Immunol. (1999) [Pubmed]
  27. Regulation of microtubule formation in activated mast cells by complexes of gamma-tubulin with Fyn and Syk kinases. Sulimenko, V., Dráberová, E., Sulimenko, T., Macurek, L., Richterová, V., Dráber, P., Dráber, P. J. Immunol. (2006) [Pubmed]
  28. Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Cornall, R.J., Cyster, J.G., Hibbs, M.L., Dunn, A.R., Otipoby, K.L., Clark, E.A., Goodnow, C.C. Immunity (1998) [Pubmed]
  29. Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors. Lannutti, B.J., Drachman, J.G. Blood (2004) [Pubmed]
  30. Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling. Liang, X., Wisniewski, D., Strife, A., Shivakrupa, n.u.l.l., Clarkson, B., Resh, M.D. J. Biol. Chem. (2002) [Pubmed]
  31. Constitutive membrane association potentiates activation of Bruton tyrosine kinase. Li, T., Rawlings, D.J., Park, H., Kato, R.M., Witte, O.N., Satterthwaite, A.B. Oncogene (1997) [Pubmed]
  32. 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. Pleiman, C.M., Clark, M.R., Gauen, L.K., Winitz, S., Coggeshall, K.M., Johnson, G.L., Shaw, A.S., Cambier, J.C. Mol. Cell. Biol. (1993) [Pubmed]
  33. The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn. Hong, H., Kitaura, J., Xiao, W., Horejsi, V., Ra, C., Lowell, C.A., Kawakami, Y., Kawakami, T. Blood (2007) [Pubmed]
  34. Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases. Corey, S.J., Burkhardt, A.L., Bolen, J.B., Geahlen, R.L., Tkatch, L.S., Tweardy, D.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  35. Microarray analysis of Lyn-deficient B cells reveals germinal center-associated nuclear protein and other genes associated with the lymphoid germinal center. Mirnics, Z.K., Caudell, E., Gao, Y., Kuwahara, K., Sakaguchi, N., Kurosaki, T., Burnside, J., Mirnics, K., Corey, S.J. J. Immunol. (2004) [Pubmed]
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