TY  - JOUR
A1  - Mori, Jun
A1  - Pearce, Andrew C.
A1  - Spalton, Jennifer C.
A1  - Grygielska, Beata
A1  - Eble, Johannes A.
A1  - Tomlinson, Michael G.
A1  - Senis, Yotis A.
A1  - Watson, Steve P.
T1  - G6b-B inhibits constitutive and agonist-induced signaling by glycoprotein VI and CLEC-2
T2  - The journal of biological chemistry
N2  - Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR γ-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cγ (PLCγ). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5′-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR γ-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation.
Y1  - 2008
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25557
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-255571
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2602894/
SN  - 0021-9258
SN  - 1083-351X
N1  - © 2008 by The American Society for Biochemistry and Molecular Biology, Inc
VL  - 283
IS  - 51
SP  - 35419
EP  - 35427
PB  - American Soc. for Biochemistry and Molecular Biology
CY  - Bethesda, Md.
ER  -