SYK, along with Zap-70, is a member of the Syk family of tyrosine kinases. These non-receptor cytoplasmic tyrosine kinases share a characteristic dual SH2 domain separated by a linker domain. However, activation of SYK relies less on phosporylation by Src family kinases than Zap-70.
While Syk and Zap-70 are primarily expressed in hematopoietic tissues, there is expression of Syk in a variety of tissues. Within B and T cells respectively, Syk and Zap-70 transmit signals from the B-Cell receptor and T-Cell receptor. Syk plays a similar role in transmitting signals from a variety of cell surface receptors including CD74, Fc Receptor, and integrins.
Mice that lack Syk completely (Syk−/−, Syk-knockout) die during embryonic development around midgestation. They show severe defects in the development of the lymphatic system. Normally, the lymphatic system and the blood system are strictly separated from each other. However, in Syk deficient mice the lymphatics and the blood vessels form abnormal shunts, leading to leakage of blood into the lymphatic system. The reason for this phenotype was identified by a genetic fate mapping approach, showing that Syk is expressed in myeloid cells which orchestrate the proper separation of lymphatics and blood system during embryogenesis and beyond. Thus, Syk is an essential regulator of the lymphatic system development in mice.
The Syk inhibitor nilvadipine has been shown to regulate amyloid-β production and Tau phosphorylation and hence has been proposed as a treatment for Alzheimer's Disease and has entered phase III clinical trials.
Without Syk, the protein it makes, and genetic disruption in a panel of 55 genes thought also to be controlled by Syk, breast ductal carcinoma in situ (breast DCIS, which can become invasive), it is believed that the cancer has a markedly increased tendency to invade and metastasize.
^Ku G, Malissen B, Mattei MG (1994). "Chromosomal location of the Syk and ZAP-70 tyrosine kinase genes in mice and humans". Immunogenetics. 40 (4): 300–2. PMID8082894. doi:10.1007/BF00189976.
^ abcdefSeda V, Mraz M (March 2015). "B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells". European Journal of Haematology. 94 (3): 193–205. PMID25080849. doi:10.1111/ejh.12427.
^Roskoski R (2016). "Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms". Pharmacological Research. 113 (Pt A): 395–408. PMID27641927. doi:10.1016/j.phrs.2016.09.011.
^ abBertagnolo V, Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi ML, Capitani S (April 2001). "Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells". Cell Growth & Differentiation. 12 (4): 193–200. PMID11331248.
^Lupher ML, Rao N, Lill NL, Andoniou CE, Miyake S, Clark EA, Druker B, Band H (December 1998). "Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323". The Journal of Biological Chemistry. 273 (52): 35273–81. PMID9857068. doi:10.1074/jbc.273.52.35273.
^Oda A, Ochs HD, Lasky LA, Spencer S, Ozaki K, Fujihara M, Handa M, Ikebuchi K, Ikeda H (May 2001). "CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk". Blood. 97 (9): 2633–9. PMID11313252. doi:10.1182/blood.V97.9.2633.
^Ibarrola I, Vossebeld PJ, Homburg CH, Thelen M, Roos D, Verhoeven AJ (July 1997). "Influence of tyrosine phosphorylation on protein interaction with FcgammaRIIa". Biochimica et Biophysica Acta. 1357 (3): 348–58. PMID9268059. doi:10.1016/S0167-4889(97)00034-7.
^Kim MK, Pan XQ, Huang ZY, Hunter S, Hwang PH, Indik ZK, Schreiber AD (January 2001). "Fc gamma receptors differ in their structural requirements for interaction with the tyrosine kinase Syk in the initial steps of signaling for phagocytosis". Clinical Immunology. 98 (1): 125–32. PMID11141335. doi:10.1006/clim.2000.4955.
^Deckert M, Elly C, Altman A, Liu YC (April 1998). "Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases". The Journal of Biological Chemistry. 273 (15): 8867–74. PMID9535867. doi:10.1074/jbc.273.15.8867.
^Chung J, Gao AG, Frazier WA (June 1997). "Thrombspondin acts via integrin-associated protein to activate the platelet integrin alphaIIbbeta3". The Journal of Biological Chemistry. 272 (23): 14740–6. PMID9169439. doi:10.1074/jbc.272.23.14740.
^ abGanju RK, Brubaker SA, Chernock RD, Avraham S, Groopman JE (June 2000). "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". The Journal of Biological Chemistry. 275 (23): 17263–8. PMID10747947. doi:10.1074/jbc.M000689200.
^Sada K, Minami Y, Yamamura H (September 1997). "Relocation of Syk protein-tyrosine kinase to the actin filament network and subsequent association with Fak". European Journal of Biochemistry. 248 (3): 827–33. PMID9342235. doi:10.1111/j.1432-1033.1997.00827.x.
^Dustin LB, Plas DR, Wong J, Hu YT, Soto C, Chan AC, Thomas ML (March 1999). "Expression of dominant-negative src-homology domain 2-containing protein tyrosine phosphatase-1 results in increased Syk tyrosine kinase activity and B cell activation". Journal of Immunology. 162 (5): 2717–24. PMID10072516.
^Deckert M, Tartare-Deckert S, Couture C, Mustelin T, Altman A (December 1996). "Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product". Immunity. 5 (6): 591–604. PMID8986718. doi:10.1016/S1074-7613(00)80273-3.
^Song JS, Gomez J, Stancato LF, Rivera J (October 1996). "Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex". The Journal of Biological Chemistry. 271 (43): 26962–70. PMID8900182. doi:10.1074/jbc.271.43.26962.
Yanagi S, Inatome R, Takano T, Yamamura H (November 2001). "Syk expression and novel function in a wide variety of tissues". Biochemical and Biophysical Research Communications. 288 (3): 495–8. PMID11676469. doi:10.1006/bbrc.2001.5788.