Murine GPVI stimulates weak integrin activation in PLC gamma 2-/- platelets: involvement of PLC gamma 1 and PI3-kinase

Research output: Contribution to journalArticle

Standard

Murine GPVI stimulates weak integrin activation in PLC gamma 2-/- platelets: involvement of PLC gamma 1 and PI3-kinase. / Suzuki-Inoue, K; Inoue, O; Frampton, Jonathan; Watson, Steve.

In: Blood, Vol. 102, No. 4, 01.08.2003, p. 1367-1373.

Research output: Contribution to journalArticle

Harvard

APA

Vancouver

Author

Bibtex

@article{36e9fae2099842ccac341563a32943a0,
title = "Murine GPVI stimulates weak integrin activation in PLC gamma 2-/- platelets: involvement of PLC gamma 1 and PI3-kinase",
abstract = "Collagen stimulates platelet activation through a tyrosine kinase-based pathway downstream of the glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex. Genetic ablation of FcR gamma-chain results in a complete inhibition of aggregation to collagen. In contrast, a steady increase in light transmission is induced by collagen in phospholipase Cgamma2-deficient (PLCgamma2(-/-)) platelets in a Born aggregometer, indicating a weak level of activation. This increase is inhibited partially in the presence of an alpha(2)beta(1)-blocking antibody or an alpha(IIb)beta(3) antagonist and completely by a combination of the 2 inhibitors. It is also abolished by the Src kinase inhibit or PIP1 and reduced in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. The GPVI-specific agonists convulxin and collagen-related peptide (PRIP) also stimulate weak aggregation in PLCgamma2(-/-) platelets, which is inhibited by wortmannin and PPI. Collagen and CRP stimulate tyrosine phosphorylation of PLCgamma1 at its regulatory site, Tyr 783, in murine but not in human platelets through a Src kinase-dependent pathway. Adhesion of PLCgamma2(-/-) platelets to a collagen monolayer is severely reduced at a shear rate of 800 s(-1), relative to controls, whereas it is abolished in FcR gamma-chain(-/-) platelets. These results provide strong evidence that engagement of GPVI stimulates limited integrin activation in PLCgamma2(-/-) platelets via PLCgamma1 and PI3-kinase. (C) 2003 by The American Society of Hematology.",
author = "K Suzuki-Inoue and O Inoue and Jonathan Frampton and Steve Watson",
year = "2003",
month = aug,
day = "1",
doi = "10.1182/blood-2003-01-0029",
language = "English",
volume = "102",
pages = "1367--1373",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "4",

}

RIS

TY - JOUR

T1 - Murine GPVI stimulates weak integrin activation in PLC gamma 2-/- platelets: involvement of PLC gamma 1 and PI3-kinase

AU - Suzuki-Inoue, K

AU - Inoue, O

AU - Frampton, Jonathan

AU - Watson, Steve

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Collagen stimulates platelet activation through a tyrosine kinase-based pathway downstream of the glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex. Genetic ablation of FcR gamma-chain results in a complete inhibition of aggregation to collagen. In contrast, a steady increase in light transmission is induced by collagen in phospholipase Cgamma2-deficient (PLCgamma2(-/-)) platelets in a Born aggregometer, indicating a weak level of activation. This increase is inhibited partially in the presence of an alpha(2)beta(1)-blocking antibody or an alpha(IIb)beta(3) antagonist and completely by a combination of the 2 inhibitors. It is also abolished by the Src kinase inhibit or PIP1 and reduced in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. The GPVI-specific agonists convulxin and collagen-related peptide (PRIP) also stimulate weak aggregation in PLCgamma2(-/-) platelets, which is inhibited by wortmannin and PPI. Collagen and CRP stimulate tyrosine phosphorylation of PLCgamma1 at its regulatory site, Tyr 783, in murine but not in human platelets through a Src kinase-dependent pathway. Adhesion of PLCgamma2(-/-) platelets to a collagen monolayer is severely reduced at a shear rate of 800 s(-1), relative to controls, whereas it is abolished in FcR gamma-chain(-/-) platelets. These results provide strong evidence that engagement of GPVI stimulates limited integrin activation in PLCgamma2(-/-) platelets via PLCgamma1 and PI3-kinase. (C) 2003 by The American Society of Hematology.

AB - Collagen stimulates platelet activation through a tyrosine kinase-based pathway downstream of the glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex. Genetic ablation of FcR gamma-chain results in a complete inhibition of aggregation to collagen. In contrast, a steady increase in light transmission is induced by collagen in phospholipase Cgamma2-deficient (PLCgamma2(-/-)) platelets in a Born aggregometer, indicating a weak level of activation. This increase is inhibited partially in the presence of an alpha(2)beta(1)-blocking antibody or an alpha(IIb)beta(3) antagonist and completely by a combination of the 2 inhibitors. It is also abolished by the Src kinase inhibit or PIP1 and reduced in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. The GPVI-specific agonists convulxin and collagen-related peptide (PRIP) also stimulate weak aggregation in PLCgamma2(-/-) platelets, which is inhibited by wortmannin and PPI. Collagen and CRP stimulate tyrosine phosphorylation of PLCgamma1 at its regulatory site, Tyr 783, in murine but not in human platelets through a Src kinase-dependent pathway. Adhesion of PLCgamma2(-/-) platelets to a collagen monolayer is severely reduced at a shear rate of 800 s(-1), relative to controls, whereas it is abolished in FcR gamma-chain(-/-) platelets. These results provide strong evidence that engagement of GPVI stimulates limited integrin activation in PLCgamma2(-/-) platelets via PLCgamma1 and PI3-kinase. (C) 2003 by The American Society of Hematology.

UR - http://www.scopus.com/inward/record.url?scp=0041737534&partnerID=8YFLogxK

U2 - 10.1182/blood-2003-01-0029

DO - 10.1182/blood-2003-01-0029

M3 - Article

C2 - 12730118

VL - 102

SP - 1367

EP - 1373

JO - Blood

JF - Blood

SN - 0006-4971

IS - 4

ER -