Syk activation leads to SLP-76 activation

Stable Identifier
R-HSA-429449
Type
Reaction [transition]
Species
Homo sapiens
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Stimulation of platelets with collagen-related peptide leads to tyrosine phosphorylation of SLP-76, an adaptor protein with multiple binding domains (Gross et al. 1999). Phosphorylation of SLP-76 is mediated by Syk, analogous to the role of ZAP-70 in phosphorylating T-cell SLP-76 (Bubeck-Wardenberg et al. 1996, Hussain et al. 1999, Fasbender et al. 2017). SLP-76 was shown to bind to tyrosine-phosphorylated C-terminal tail of SYK (de Castro et al. 2012). The phosphorylated tyrosine residues provide a binding site for the SH2 domains of downstream signalling proteins like Vav, Itk and ADAP (Jordan et al. 2003). Platelets from mice defective in SLP76 do not connect GPVI engagement with downstream signaling (Clements et al. 1999, Judd et al. 2000). GPVI signaling via SLP-76 does not appear to require LAT or GADS (Judd et al. 2002) suggesting that the mechanism is not identical to that of T-cells. LAT and SLP-76 are both required for P-selectin expression and degranulation but may function independently, or rely on proteins not required by T-cells (Jordan et al. 2003).

Literature References
PubMed ID Title Journal Year
10026222 Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets

Gross, BS, Lee, JR, Clements, JL, Turner, M, Tybulewicz, VL, Findell, PR, Koretzky, GA, Watson, SP

J Biol Chem 1999
28736554 Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes

Fasbender, F, Claus, M, Wingert, S, Sandusky, M, Watzl, C

Front Immunol 2017
19850008 Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein

Hussain, A, Faryal, R, Nore, BF, Mohamed, AJ, Smith, CI

Biochem. Biophys. Res. Commun. 2009
22267732 Once phosphorylated, tyrosines in carboxyl terminus of protein-tyrosine kinase Syk interact with signaling proteins, including TULA-2, a negative regulator of mast cell degranulation

de Castro, RO, Zhang, J, Groves, JR, Barbu, EA, Siraganian, RP

J. Biol. Chem. 2012
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Title
protein tyrosine kinase activity of p-Y348-SYK [cytosol]
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Orthologous Events
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