Reactome | Unknown kinase phosphorylates CLEC1B dimer:PDPN

Unknown kinase phosphorylates CLEC1B dimer:PDPN

Stable Identifier

R-HSA-5684806

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Unknown kinase phosphorylates CLEC1B dimer:PDPN

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Following stimulation by rhodocytin CLEC1B is phosphorylated on the YxxL or hemi-ITAM motif. The kinase responsible for this is not clear. Phosphorylation is suggested to allow the tandem SH2 domains of SYK to bind phosphorylated CLEC1B hemi-ITAM sites (Suzuki-Inoue et al. 2006). GPVI ITAMs are phosphorylated by the Src family kinases FYN and LYN, which results in SYK binding, but CLEC1B appears to be phosphorylated mainly by SYK. The SYK-specific inhibitor R406 inhibits CLEC1B phosphorylation in response to rhodocytin, suggesting SYK is responsible for hemi-ITAM phosphorylation in human platelets (Spalton et al. 2009). However the Src family-specific kinase inhibitor PP2 also inhibits CLEC1B tyrosine phosphorylation (Suzuki-Inoue et al. 2006), suggesting that CLEC1B is phosphorylated by Syk and Src family kinases in human platelets (Suzuki-Inoue et al. 2006, Suzuki-Inoue 2011). Severin et al. (2011) reported that phosphorylation of CLEC1B by rhodocytin is abolished in Syk-deficient mice, while phosphorylation is not altered in mice deficient in the major platelet Src family kinases Fyn, Lyn, Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. The same group also reported that PP2 does not inhibit phosphorylation of mouse Clec1b by rhodocytin, in contrast to the reported effect in human platelets (Suzuki-Inoue et al. 2006), suggesting that Syk phosphorylates Clec1b independently of the Src family kinases in mice.

Literature References

PubMed ID	Title	Journal	Year
16174766	A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2 Theakston, RD, Watson, SP, Suzuki-Inoue, K, Eble, JA, Ozaki, Y, Morita, T, Schweighoffer, E, Pearce, AC, Hughan, SC, García, A, Inoue, O, Tybulewicz, VL, Pöhlmann, S, Zitzmann, N, Gartner, TK, Laing, GD, Fuller, GL	Blood	2006