Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
Blood. 2011 Apr 7;117(14):3903-6. doi: 10.1182/blood-2010-09-304816. Epub 2011 Feb 4.
Inhibition of platelet responsiveness is important to control pathologic thrombus formation. Platelet-endothelial cell adhesion molecule-1 (PECAM-1) and the Src family kinase Lyn inhibit platelet activation by the glycoprotein VI (GPVI) collagen receptor; however, it is not known whether PECAM-1 and Lyn function in the same or different inhibitory pathways. In these studies, we found that, relative to wild-type platelets, platelets derived from PECAM-1-deficient, Lyn-deficient, or PECAM-1/Lyn double-deficient mice were equally hyperresponsive to stimulation with a GPVI-specific agonist, indicating that PECAM-1 and Lyn participate in the same inhibitory pathway. Lyn was required for PECAM-1 tyrosine phosphorylation and subsequent binding of the Src homology 2 domain-containing phosphatase-2, SHP-2. These results support a model in which PECAM-1/SHP-2 complexes, formed in a Lyn-dependent manner, suppress GPVI signaling.
抑制血小板反应性对于控制病理性血栓形成非常重要。血小板内皮细胞黏附分子-1（PECAM-1）和Src 家族激酶 Lyn 通过糖蛋白 VI（GPVI）胶原受体抑制血小板活化；然而，PECAM-1 和 Lyn 是否在相同或不同的抑制途径中发挥作用尚不清楚。在这些研究中，我们发现，与野生型血小板相比，源自 PECAM-1 缺陷型、Lyn 缺陷型或 PECAM-1/Lyn 双缺陷型小鼠的血小板对 GPVI 特异性激动剂的刺激反应性相等，表明 PECAM-1 和 Lyn 参与相同的抑制途径。Lyn 是 PECAM-1 酪氨酸磷酸化和随后结合含有Src 同源 2 结构域的磷酸酶-2（SHP-2）所必需的。这些结果支持这样一种模型，即 PECAM-1/SHP-2 复合物以 Lyn 依赖性方式形成，从而抑制 GPVI 信号。
