Collagen-like peptide stimulates tyrosine phosphorylation of syk and phospholipase C gamma 2 in platelets independent of the integrin alpha(2)beta(1)
Collagen-like peptide stimulates tyrosine phosphorylation of syk and phospholipase C gamma 2 in platelets independent of the integrin alpha(2)beta(1)
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DOI：
10.1182/blood.v89.4.1235
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发表时间：
1997-02-15
期刊：
影响因子：
20.3
通讯作者：
Watson, SP
中科院分区：
文献类型：
--
作者：
Asselin, J;Gibbins, JM;Watson, SP
胶原蛋白通过依赖酪氨酸激酶的途径激活血小板，该途径与Pc受体伽马链、酪氨酸激酶SYK和磷脂酶C伽马2(PLC Gamma 2)的磷酸化有关。我们最近描述了一种胶原相关的三螺旋多肽(CRP)，序列为GCP*(GPP*)GCP*G(单字母氨基酸编码：P*=羟脯氨酸；Morton等，Biochem J 306：337,1995)。交联肽是血小板激活的有力刺激，但与胶原不同，它不支持α(2)β(1)介导的、依赖于镁离子的黏附，这表明它的作用独立于整合素α(2)β(1)。这一发现表明存在一种血小板受体，而不是α(2)β(1)，它是激活的基础。在目前的研究中，我们发现，CRP刺激与胶原蛋白相同模式的蛋白质的酪氨酸磷酸化，包括SYK和PLC Gamma 2。在没有镁离子或整合素α(2)β(1)(Moab 6F1和Moab 13)的单抗存在的情况下，CRP诱导的蛋白质酪氨酸磷酸化不会改变，这些条件阻止了胶原与整合素的相互作用。相反，Moab 6F1和Moab 13或通过去除Mg2+部分减少了胶原对SYK和PLC Gamma 2的磷酸化。这可能反映了α(2)β(1)在胶原诱导的信号事件中的直接作用，或者是整合素促进胶原与其信号受体结合的间接作用。结果表明，CRP激活血小板的途径不依赖于α(2)、β(1)，其中包括SYK和PLC-γ2的磷酸化。这一途径似乎有助于胶原对血小板的激活。(C)1997年由美国血液病学会主办。
Activation of platelets by collagen is mediated through a tyrosine kinase-dependent pathway that is associated with phosphorylation of the Pc receptor gamma chain, the tyrosine kinase syk, and phospholipase C gamma 2 (PLC gamma 2). We recently described a collagen-related triple-helical peptide (CRP) with the sequence GCP*(GPP*)GCP*G (single letter amino acid code: P* = hydroxyproline; Morton et al, Biochem J 306:337, 1995). The cross-linked peptide is a potent stimulus of platelet activation but, unlike collagen, does not support alpha(2) beta(1)-mediated, Mg2+-dependent adhesion, suggesting that its action is independent of the integrin alpha(2) beta(1). This finding suggests the existence of a platelet receptor other than alpha(2) beta(1) that underlies activation. In the present study, we show that CRP stimulates tyrosine phosphorylation of the same pattern of proteins in platelets as collagen, including syk and PLC gamma 2. Protein tyrosine phosphorylation induced by CRP is not altered in the absence of Mg2+ or the presence of monoclonal antibodies (MoAbs) to the integrin alpha(2) beta(1) (MoAb 6F1 and MoAb 13), conditions that prevent the interaction of collagen with the integrin. In contrast, phosphorylation of syk and PLC gamma 2 by collagen is partially reduced by MoAb 6F1 and MoAb 13 or by removal of Mg2+. This may reflect a direct role of alpha(2) beta(1) in collagen-induced signaling events or an indirect role in which the integrin facilitates the binding of collagen to its signaling receptor. The results show an alpha(2) beta(1)-independent pathway of platelet activation by CRP that involves phosphorylation of syk and PLC gamma 2. This pathway appears to contribute to platelet activation by collagen. (C) 1997 by The American Society of Hematology.