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Gene Review

Syk  -  spleen tyrosine kinase

Rattus norvegicus

Synonyms: Spleen tyrosine kinase, Tyrosine-protein kinase SYK, p72Syk
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Disease relevance of Syk

  • Importantly, tamalin was endogenously phosphorylated and associated with Syk in retinoic acid-treated P19 embryonal carcinoma cells that undergo neuron-like differentiation [1].
  • Additionally, Syk ASO suppressed Ag-induced pulmonary inflammation, suggesting that Syk ASO may prove useful as an anti-inflammatory therapy in disorders such as asthma [2].
  • We show that compound 48/80 (c48/80), a receptor analogue that activates directly G proteins, activates Syk in a pertussis toxin-sensitive fashion [3].
  • Syk ASO, delivered in a liposome, carrier/lipid complex by aerosol to rats, significantly inhibited the Ag-induced inflammatory cell infiltrate in the bronchoalveolar space, decreasing both neutrophilia and eosinophilia [4].
  • We isolated from a phage display library human single-chain variable fragments (scFv) directed against the portion of Syk containing the Src homology 2 domains and the linker region that separates them [5].

High impact information on Syk


Biological context of Syk

  • Phosphorylation and recruitment of Syk by immunoreceptor tyrosine-based activation motif-based phosphorylation of tamalin [1].
  • Our results provide a molecular mechanism for down-regulation of engaged receptor complexes by targeting ubiquitinated FcepsilonRI and activated Syk to the proteasome for degradation [8].
  • Syk, recruited to the clustered BCR, becomes phosphorylated on three tyrosines (Tyr-317, Tyr-342, and Tyr-346) located within the linker region that separates the C-terminal catalytic domain from the N-terminal tandem Src homology 2 domains [9].
  • By transfection, cloned lines were established with stable expression of Syk [6].
  • Competitive binding studies with coelectroporated unlabeled Syk, PLC-gamma1, and other SH2 domains selectively suppressed the induction of IgE receptor-mediated calcium signals as well as the binding of the fluorescent SH2 domains [10].

Anatomical context of Syk

  • Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc epsilon RI signaling in mast cells [11].
  • This requirement was demonstrated by overexpression of Syk wild-type or its kinase-dead mutant in RBL cells or using an Syk-deficient RBL-derived cell line transfected with wild-type or a kinase inactive form of Syk [8].
  • Regulation of signaling in B cells through the phosphorylation of Syk on linker region tyrosines. A mechanism for negative signaling by the Lyn tyrosine kinase [9].
  • Thus, these in vivo studies support a plasma membrane signaling mechanism by which IgE receptors transiently associate with microdomains and induce the spatially restricted activation of Syk and PLC-gamma1 [10].
  • Chimeric Syk with the myristylation sequence was membrane associated, and a small fraction was constitutively colocalized with FcepsilonRI, Lyn, and LAT (linker for T-cell activation) in the glycolipid-enriched microdomains or rafts [12].

Associations of Syk with chemical compounds

  • Syk with Y342F mutation failed to reconstitute Fc epsilon RI-initiated histamine release [11].
  • Alpha-MSH and the Syk kinase inhibitor piceatannol blocked these processes [13].
  • Thus, Syk and Lyn combine to determine the pathway through which the BCR is coupled to Ca(2+) mobilization as well as the magnitude and duration of the Ca(2+) flux [9].
  • Syk that is not phosphorylated on linker region tyrosines couples the BCR to Ca(2+) mobilization through a phosphoinositide 3-kinase-dependent pathway [9].
  • Requirement for a negative charge at threonine 60 of the FcRgamma for complete activation of Syk [14].

Physical interactions of Syk

  • A fusion protein containing Src homology 2 (SH2) and SH3 domains of Lyn bound Syk from lysates of nonactivated RBL cells; an increased binding was observed when lysates from Ag- or pervanadate-activated cells were used [15].

Enzymatic interactions of Syk

  • Further experiments have indicated that Syk-Lyn interactions occur in Ag-activated RBL cells under in vivo conditions and that these interactions could involve direct binding of the Lyn SH2 domain with phosphorylated tyrosine of Syk [15].
  • Here we report that Syk is also rapidly tyrosine phosphorylated upon Thy-1 cross-linking [16].

Regulatory relationships of Syk


Other interactions of Syk


Analytical, diagnostic and therapeutic context of Syk

  • To examine the role of Syk in the Fc epsilon RI signaling pathway, we identified a variant of RBL-2H3 cells that has no detectable Syk by immunoblotting and by in vitro kinase reactions [6].
  • This correlated with reduced co-immunoprecipitation of FcepsilonRIgamma with Syk [14].
  • RT-PCR and RT-in situ PCR demonstrated that aerosolized Syk ASO administration reduced Syk mRNA expression from alveolar macrophages compared with cells isolated from sham-treated rats [2].
  • Western blot analysis confirmed that Syk PTK expression was reduced after Syk ASO treatment [2].
  • Immunogold electron microscopy showed that H10-FcepsilonRI dimers colocalize preferentially with Lyn and are rarely within the osmiophilic "signaling domains" that accumulate FcepsilonRI and Syk in Ag-treated cells [22].


  1. Phosphorylation and recruitment of Syk by immunoreceptor tyrosine-based activation motif-based phosphorylation of tamalin. Hirose, M., Kitano, J., Nakajima, Y., Moriyoshi, K., Yanagi, S., Yamamura, H., Muto, T., Jingami, H., Nakanishi, S. J. Biol. Chem. (2004) [Pubmed]
  2. Aerosolized Syk antisense suppresses Syk expression, mediator release from macrophages, and pulmonary inflammation. Stenton, G.R., Kim, M.K., Nohara, O., Chen, C.F., Hirji, N., Wills, F.L., Gilchrist, M., Hwang, P.H., Park, J.G., Finlay, W., Jones, R.L., Befus, A.D., Schreiber, A.D. J. Immunol. (2000) [Pubmed]
  3. Gi-mediated activation of the Syk kinase by the receptor mimetic basic secretagogues of mast cells: role in mediating arachidonic acid/metabolites release. Shefler, I., Sagi-Eisenberg, R. J. Immunol. (2001) [Pubmed]
  4. Inhibition of allergic inflammation in the airways using aerosolized antisense to Syk kinase. Stenton, G.R., Ulanova, M., Déry, R.E., Merani, S., Kim, M.K., Gilchrist, M., Puttagunta, L., Musat-Marcu, S., James, D., Schreiber, A.D., Befus, A.D. J. Immunol. (2002) [Pubmed]
  5. Intracellular single-chain variable fragments directed to the Src homology 2 domains of Syk partially inhibit Fc epsilon RI signaling in the RBL-2H3 cell line. Dauvillier, S., Mérida, P., Visintin, M., Cattaneo, A., Bonnerot, C., Dariavach, P. J. Immunol. (2002) [Pubmed]
  6. Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells. Zhang, J., Berenstein, E.H., Evans, R.L., Siraganian, R.P. J. Exp. Med. (1996) [Pubmed]
  7. High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc(epsilon)RI and LAT. Wilson, B.S., Pfeiffer, J.R., Surviladze, Z., Gaudet, E.A., Oliver, J.M. J. Cell Biol. (2001) [Pubmed]
  8. Activation of Syk tyrosine kinase is required for c-Cbl-mediated ubiquitination of Fcepsilon RI and Syk in RBL cells. Paolini, R., Molfetta, R., Beitz, L.O., Zhang, J., Scharenberg, A.M., Piccoli, M., Frati, L., Siraganian, R., Santoni, A. J. Biol. Chem. (2002) [Pubmed]
  9. Regulation of signaling in B cells through the phosphorylation of Syk on linker region tyrosines. A mechanism for negative signaling by the Lyn tyrosine kinase. Hong, J.J., Yankee, T.M., Harrison, M.L., Geahlen, R.L. J. Biol. Chem. (2002) [Pubmed]
  10. Compartmentalized IgE receptor-mediated signal transduction in living cells. Stauffer, T.P., Meyer, T. J. Cell Biol. (1997) [Pubmed]
  11. Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc epsilon RI signaling in mast cells. Zhang, J., Berenstein, E., Siraganian, R.P. Mol. Cell. Biol. (2002) [Pubmed]
  12. SH2 domain-mediated targeting, but not localization, of Syk in the plasma membrane is critical for FcepsilonRI signaling. Sada, K., Zhang, J., Siraganian, R.P. Blood (2001) [Pubmed]
  13. Alpha-melanocyte stimulating hormone protects against H2O2-induced inhibition of wound restitution in IEC-6 cells via a Syk kinase- and NF-kappabeta-dependent mechanism. Zou, L., Sato, N., Kone, B.C. Shock (2004) [Pubmed]
  14. Requirement for a negative charge at threonine 60 of the FcRgamma for complete activation of Syk. Swann, P.G., Odom, S., Zhou, Y.J., Szallasi, Z., Blumberg, P.M., Draber, P., Rivera, J. J. Biol. Chem. (1999) [Pubmed]
  15. Direct interaction of Syk and Lyn protein tyrosine kinases in rat basophilic leukemia cells activated via type I Fc epsilon receptors. Amoui, M., Dráberová, L., Tolar, P., Dráber, P. Eur. J. Immunol. (1997) [Pubmed]
  16. Protein tyrosine kinase Syk is involved in Thy-1 signaling in rat basophilic leukemia cells. Tolar, P., Dráberová, L., Dráber, P. Eur. J. Immunol. (1997) [Pubmed]
  17. Activation of the high-affinity immunoglobulin E receptor Fc epsilon RI in RBL-2H3 cells is inhibited by Syk SH2 domains. Taylor, J.A., Karas, J.L., Ram, M.K., Green, O.M., Seidel-Dugan, C. Mol. Cell. Biol. (1995) [Pubmed]
  18. The protein tyrosine kinase syk activity is reduced by clustering the mast cell function-associated antigen. Xu, R., Pecht, I. Eur. J. Immunol. (2001) [Pubmed]
  19. Cutting edge: extracellular signal-regulated kinase activates syk: a new potential feedback regulation of Fc epsilon receptor signaling. Xu, R., Seger, R., Pecht, I. J. Immunol. (1999) [Pubmed]
  20. Syk-dependent phosphorylation of Shc. A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2. Jabril-Cuenod, B., Zhang, C., Scharenberg, A.M., Paolini, R., Numerof, R., Beaven, M.A., Kinet, J.P. J. Biol. Chem. (1996) [Pubmed]
  21. Activation of macrophage CD8: pharmacological studies of TNF and IL-1 beta production. Lin, T.J., Hirji, N., Stenton, G.R., Gilchrist, M., Grill, B.J., Schreiber, A.D., Befus, A.D. J. Immunol. (2000) [Pubmed]
  22. Overcoming the signaling defect of Lyn-sequestering, signal-curtailing FcepsilonRI dimers: aggregated dimers can dissociate from Lyn and form signaling complexes with Syk. Lara, M., Ortega, E., Pecht, I., Pfeiffer, J.R., Martinez, A.M., Lee, R.J., Surviladze, Z., Wilson, B.S., Oliver, J.M. J. Immunol. (2001) [Pubmed]
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