Reactome | Syk activation leads to SLP-76 activation

Syk activation leads to SLP-76 activation

Stable Identifier

R-HSA-429449

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Syk activation leads to SLP-76 activation

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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
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
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
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