Monomeric (glycine-proline-hydroxyproline)10 repeat sequence is a partial agonist of the platelet collagen receptor glycoprotein VI
Monomeric (glycine-proline-hydroxyproline)10 repeat sequence is a partial agonist of the platelet collagen receptor glycoprotein VI
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DOI：
10.1042/0264-6021:3390413
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发表时间：
1999-04-15
影响因子：
4.1
通讯作者：
Watson, SP
中科院分区：
文献类型：
--
作者：
Asselin, J;Knight, CG;Watson, SP
我们先前已经报道，一种三螺旋胶原相关多肽(CRP；也称为CRP-XL)，含有甘氨酸-脯氨酸-羟脯氨酸(GPP*)重复基序，并通过其N端和C端的半胱氨酸残基交联，通过表面受体糖蛋白VI(GPVI)强烈刺激血小板聚集和分泌。血小板的激活与酪氨酸激酶Syk和磷脂酶C-Gamma 2(PLC-Gamma 2)的酪氨酸磷酸化有关。我们现在报道，CRP的非交联型骨架单体CRP(MCRP)刺激血小板Syk和PLC Gam2的酪氨酸磷酸化，并诱导[H-3]5-羟色胺([H-3]5-HT)的弱分泌和聚集。MCRP的作用似乎不是由于自发的交联，因为半胱氨酸残基的烷基化导致活性的增加。C反应蛋白的三肽骨架GPP(10)(*)(其中P*代表羟脯氨酸)也能刺激血小板形状的改变和Syk和PLC-Gamma 2的微弱酪氨酸磷酸化，但不能诱导聚集或分泌。这些单体多肽部分抑制C反应蛋白释放[H-3]S-羟色胺，提示它们是胶原受体GPVI的部分激动剂。这些结果表明，以重复基序形式存在的GPP*足以激活血小板胶原受体GPVI，但单体的交联会导致活性的增加。
We have previously reported that a triple-helical, collagen-related peptide (CRP; also known as CRP-XL) containing a glycine-proline-hydroxyproline (GPP*) repeat motif and cross-linked through cysteine residues at its N-terminus and C-terminus is a powerful stimulus of platelet aggregation and secretion through the surface receptor glycoprotein VI (GPVI). The activation of platelets is associated with tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase C gamma 2 (PLC gamma 2). We now report that the non-cross-linked backbone of CRP, monomeric CRP (mCRP), stimulates the tyrosine phosphorylation of Syk and PLC gamma 2 in platelets and induces the weak secretion of [H-3]5-hydroxytryptamine ([H-3]5-HT) and aggregation. The action of mCRP does not seem to be due to spontaneous cross-linking, because alkylation of the cysteine residues leads to an increase in activity. The tripeptide backbone of CRP, GPP(10)(*) (in which P* represents hydroxyproline) also stimulates platelet shape change and the weak tyrosine phosphorylation of Syk and PLC gamma 2, but is unable to induce aggregation or secretion. The monomeric peptides partly inhibit the release of [H-3]S-HT by CRP, suggesting that they are partial agonists of the collagen receptor GPVI. These results demonstrate that GPP* present as a repeat motif is sufficient to activate the platelet collagen receptor GPVI but that the cross-linking of monomers brings about an increase in activity.