TY  - JOUR
A1  - Séverin, Sonia
A1  - Pollitt, Alice Y.
A1  - Navarro-Nuñez, Leyre
A1  - Nash, Craig A.
A1  - Mourão-Sá, Diego
A1  - Eble, Johannes A.
A1  - Senis, Yotis A.
A1  - Watson, Steve P.
T1  - Syk-dependent phosphorylation of CLEC-2 : a novel mechanism of hem-immunoreceptor tyrosine-based activation motif signaling
T2  - The journal of biological chemistry
N2  - The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors.
Y1  - 2010
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27456
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-274567
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039337/
SN  - 0021-9258
SN  - 1083-351X
N1  - Copyright © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Author's Choice—Final version full access.Creative Commons Attribution Non-Commercial License applies to Author Choice Articles http://creativecommons.org/licenses/by-nc/3.0/
VL  - 286
IS  - 6
SP  - 4107
EP  - 4116
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda, Md.
ER  -