Murine GPVI stimulates weak integrin activation in PLCgamma2-/- platelets: involvement of PLCgamma1 and PI3-kinase.
Murine GPVI stimulates weak integrin activation in PLCgamma2-/- platelets: involvement of PLCgamma1 and PI3-kinase.
复制标题
鼠 GPVI 刺激 PLCgamma2-/- 血小板中的弱整合素激活：PLCgamma1 和 PI3-激酶的参与。
作者：
K. Suzuki;O. Inoue;J. Frampton;S. Watson
胶原蛋白通过糖蛋白VI（GPVI）-Fc受体（FcR）γ链复合物下游的酪氨酸激酶途径刺激血小板活化。FcR γ-链的基因消融导致胶原蛋白聚集的完全抑制。相反，在Born凝集仪中，磷脂酶C γ 2缺陷（PLC γ 2-/-）血小板中的胶原蛋白诱导透光率稳定增加，表明激活水平较弱。这种增加在α 2 β 1阻断抗体或α IIb β 3拮抗剂存在下被部分抑制，并被2种抑制剂的组合完全抑制。它也被Src激酶抑制剂PP 1消除，并在磷脂酰肌醇（PI）3-激酶抑制剂渥曼青霉素存在下减少。GPVI特异性激动剂惊厥素和胶原相关肽（CRP）也刺激PLC γ 2-/-血小板中的弱聚集，其被渥曼青霉素和PP 1抑制。胶原蛋白和CRP通过Src激酶依赖性途径刺激小鼠血小板中PLC γ 1在其调节位点Tyr 783的酪氨酸磷酸化，但不刺激人血小板中的酪氨酸磷酸化。相对于对照组，在800 s-1的剪切速率下，PLC γ 2-/-血小板与胶原单层的粘附严重减少，而FcR γ链-/-血小板中的粘附被消除。这些结果提供了强有力的证据，即GPVI的参与通过PLC γ 1和PI 3-激酶刺激PLC γ 2-/-血小板中有限的整合素活化。
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 alpha2beta1-blocking antibody or an alphaIIbbeta3 antagonist and completely by a combination of the 2 inhibitors. It is also abolished by the Src kinase inhibitor PP1 and reduced in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. The GPVI-specific agonists convulxin and collagen-related peptide (CRP) also stimulate weak aggregation in PLCgamma2-/- platelets, which is inhibited by wortmannin and PP1. 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.
功能受损的人血小板中磷脂酶 C-β2 同工酶的表达减少。
影响因子：
20.3
作者：
Lee,SB;Rao,AK;Lee,KH;Yang,X;Bae,YS;Rhee,SG
通讯作者：
Rhee,SG
影响因子：
20.3
作者：
Lynn Quek;J. Pasquet;Ingeborg Hers;R. Cornall;Graham Knight;Mike Barnes;Margaret L. Hibbs;Ashley R. Dunn;Clifford A. Lowell;Steve P. Watson
通讯作者：
Lynn Quek;J. Pasquet;Ingeborg Hers;R. Cornall;Graham Knight;Mike Barnes;Margaret L. Hibbs;Ashley R. Dunn;Clifford A. Lowell;Steve P. Watson
影响因子：
32.4
作者：
Wang, DM;Feng, J;Ihle, JN
通讯作者：
Ihle, JN