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Gene Review

SYK  -  spleen tyrosine kinase

Homo sapiens

Synonyms: Spleen tyrosine kinase, Tyrosine-protein kinase SYK, p72-Syk
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Disease relevance of SYK


High impact information on SYK

  • Investigating possible interference of BCR-ABL1 with pre-B cell receptor signaling, we found that neither SYK nor SLP65 can be phosphorylated in response to pre-B cell receptor engagement [5].
  • Tyrosine kinase SYK: essential functions for immunoreceptor signalling [6].
  • Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein [7].
  • Using bisulfite genomic sequencing we found that in microdissected HRS cells of primary cHL SYK, BOB.1/OBF.1, and CD79B promoters were also hypermethylated [8].
  • Importantly, leukocyte rolling on P-selectin induced the recruitment of spleen tyrosine kinase (Syk), a tyrosine kinase associated to lipid raft PSGL-1 [9].

Chemical compound and disease context of SYK


Biological context of SYK


Anatomical context of SYK

  • Since lethally irradiated mice reconstituted with SYK-deficient fetal liver-derived lymphohematopoietic progenitor cells show a block in B-cell ontogeny at the pro-B to pre-B cell transition, we examined the SYK expression profiles of primary leukemic cells from children with pro-B cell ALL [2].
  • Closely related molecules with overlapping functions, such as the Syk kinases, SYK, and ZAP-70, and adaptor molecules, SH2 domain-containing leukocyte protein of 76 kDa and B cell linker protein, are expressed in activated NK cells and are all recruited to the center of the cytolytic synapse [16].
  • Spleen tyrosine kinase (Syk) is a candidate tumor (metastasis) suppressor that is highly expressed in mammary epithelial cells [17].
  • SYK, a candidate tumor suppressor, has been found not expressed in a subset of breast cancer cell lines, but the mechanism by which SYK is silenced is unclear [18].

Associations of SYK with chemical compounds

  • A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase [19].
  • Treatment of cells with a methylation inhibitor, 5-aza-2'-deoxycytidine, led to a reactivation of SYK expression in SYK-negative cells, as detected by reverse transcription-PCR [18].
  • NHERF tumorigenic mutations decreased or abolished its interaction with SYK or MERLIN, suggesting a pathway link among these three molecules that may play a critical role in mammary neoplastic progression [20].
  • This decreased invasiveness by AZA treatment was diminished by piceatannol, a SYK inhibitor, suggesting that SYK play a significant role in AZA-inducible invasion suppression [10].
  • In all five translocation-positive cases, the breakpoints were identical fusing the N-terminal pleckstrin homology domain and proline-rich region of ITK to the tyrosine kinase domain of SYK [21].

Other interactions of SYK


Analytical, diagnostic and therapeutic context of SYK

  • The patients with methylated SYK in neoplastic tissues had a significantly lower overall survival rate after hepatectomy than those with unmethylated SYK [13].
  • Gene-targeting studies have identified the cell types that require SYK for development and function, and the receptors that use SYK as well as their downstream signalling effectors [6].
  • Using methylation-specific PCR, we demonstrated that SYK is hypermethylated in 32% (12/37) of unselected breast tumors, whereas all of the matched neighboring normal breast tissues exhibited unmethylated DNA status [18].
  • Fc receptor gamma-chain and spleen tyrosine kinase (Syk) were immunoprecipitated from the lysate of platelets stimulated by vWF plus ristocetin and then analyzed by antiphosphotyrosine immunoblotting [24].


  1. Thrombspondin acts via integrin-associated protein to activate the platelet integrin alphaIIbbeta3. Chung, J., Gao, A.G., Frazier, W.A. J. Biol. Chem. (1997) [Pubmed]
  2. Spleen tyrosine kinase (Syk) deficiency in childhood pro-B cell acute lymphoblastic leukemia. Goodman, P.A., Wood, C.M., Vassilev, A., Mao, C., Uckun, F.M. Oncogene (2001) [Pubmed]
  3. Defective expression of the T-cell receptor-CD3 zeta chain in T-cell acute lymphoblastic leukaemia. Torelli, G.F., Paolini, R., Tatarelli, C., Soriani, A., Vitale, A., Guarini, A., Santoni, A., Foa, R. Br. J. Haematol. (2003) [Pubmed]
  4. Promoter hypermethylation of the 14-3-3 sigma, SYK and CAGE-1 genes is related to the various phenotypes of urinary bladder carcinomas and associated with progression of transitional cell carcinomas. Kunze, E., Wendt, M., Schlott, T. Int. J. Mol. Med. (2006) [Pubmed]
  5. Mimicry of a constitutively active pre-B cell receptor in acute lymphoblastic leukemia cells. Feldhahn, N., Klein, F., Mooster, J.L., Hadweh, P., Sprangers, M., Wartenberg, M., Bekhite, M.M., Hofmann, W.K., Herzog, S., Jumaa, H., Rowley, J.D., Müschen, M. J. Exp. Med. (2005) [Pubmed]
  6. Tyrosine kinase SYK: essential functions for immunoreceptor signalling. Turner, M., Schweighoffer, E., Colucci, F., Di Santo, J.P., Tybulewicz, V.L. Immunol. Today (2000) [Pubmed]
  7. Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein. Sidorenko, S.P., Law, C.L., Chandran, K.A., Clark, E.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Ushmorov, A., Leithäuser, F., Sakk, O., Weinhaüsel, A., Popov, S.W., Möller, P., Wirth, T. Blood (2006) [Pubmed]
  9. Lipid raft adhesion receptors and Syk regulate selectin-dependent rolling under flow conditions. Abbal, C., Lambelet, M., Bertaggia, D., Gerbex, C., Martinez, M., Arcaro, A., Schapira, M., Spertini, O. Blood (2006) [Pubmed]
  10. Reactivation of SYK expression by inhibition of DNA methylation suppresses breast cancer cell invasiveness. Yuan, Y., Liu, H., Sahin, A., Dai, J.L. Int. J. Cancer (2005) [Pubmed]
  11. Spleen tyrosine kinase (syk), a novel target of curcumin, is required for B lymphoma growth. Gururajan, M., Dasu, T., Shahidain, S., Jennings, C.D., Robertson, D.A., Rangnekar, V.M., Bondada, S. J. Immunol. (2007) [Pubmed]
  12. Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q. Gibson, S., Leung, B., Squire, J.A., Hill, M., Arima, N., Goss, P., Hogg, D., Mills, G.B. Blood (1993) [Pubmed]
  13. Frequent epigenetic inactivation of spleen tyrosine kinase gene in human hepatocellular carcinoma. Yuan, Y., Wang, J., Li, J., Wang, L., Li, M., Yang, Z., Zhang, C., Dai, J.L. Clin. Cancer Res. (2006) [Pubmed]
  14. Comparative FISH mapping on Z chromosomes of chicken and Japanese quail. Suzuki, T., Kansaku, N., Kurosaki, T., Shimada, K., Zadworny, D., Koide, M., Mano, T., Namikawa, T., Matsuda, Y. Cytogenet. Cell Genet. (1999) [Pubmed]
  15. Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation. Chen, L., Juszczynski, P., Takeyama, K., Aguiar, R.C., Shipp, M.A. Blood (2006) [Pubmed]
  16. Spatial organization of signal transduction molecules in the NK cell immune synapses during MHC class I-regulated noncytolytic and cytolytic interactions. Vyas, Y.M., Mehta, K.M., Morgan, M., Maniar, H., Butros, L., Jung, S., Burkhardt, J.K., Dupont, B. J. Immunol. (2001) [Pubmed]
  17. Alternative splicing disrupts a nuclear localization signal in spleen tyrosine kinase that is required for invasion suppression in breast cancer. Wang, L., Duke, L., Zhang, P.S., Arlinghaus, R.B., Symmans, W.F., Sahin, A., Mendez, R., Dai, J.L. Cancer Res. (2003) [Pubmed]
  18. Hypermethylation leads to silencing of the SYK gene in human breast cancer. Yuan, Y., Mendez, R., Sahin, A., Dai, J.L. Cancer Res. (2001) [Pubmed]
  19. A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase. Atwell, S., Adams, J.M., Badger, J., Buchanan, M.D., Feil, I.K., Froning, K.J., Gao, X., Hendle, J., Keegan, K., Leon, B.C., Müller-Dieckmann, H.J., Nienaber, V.L., Noland, B.W., Post, K., Rajashankar, K.R., Ramos, A., Russell, M., Burley, S.K., Buchanan, S.G. J. Biol. Chem. (2004) [Pubmed]
  20. NHERF (Na+/H+ exchanger regulatory factor) gene mutations in human breast cancer. Dai, J.L., Wang, L., Sahin, A.A., Broemeling, L.D., Schutte, M., Pan, Y. Oncogene (2004) [Pubmed]
  21. Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. Streubel, B., Vinatzer, U., Willheim, M., Raderer, M., Chott, A. Leukemia (2006) [Pubmed]
  22. Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex. Law, C.L., Sidorenko, S.P., Chandran, K.A., Draves, K.E., Chan, A.C., Weiss, A., Edelhoff, S., Disteche, C.M., Clark, E.A. J. Biol. Chem. (1994) [Pubmed]
  23. Epigenetic silencing of novel tumor suppressors in malignant melanoma. Muthusamy, V., Duraisamy, S., Bradbury, C.M., Hobbs, C., Curley, D.P., Nelson, B., Bosenberg, M. Cancer Res. (2006) [Pubmed]
  24. Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions. Goto, S., Tamura, N., Handa, S., Arai, M., Kodama, K., Takayama, H. Circulation (2002) [Pubmed]
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