Kroll M H, Hellums J D, Guo Z, Durante W, Razdan K, Hrbolich J K, Schafer A I
Veterans Affairs Medical Center, Houston, Texas 77001.
J Biol Chem. 1993 Feb 15;268(5):3520-4.
High levels of fluid shear stress at the blood vessel wall directly stimulate von Willebrand factor (vWF)-mediated platelet adhesion and aggregation and thereby contribute to the pathogenesis of arterial thrombosis. We have found that a pathological level of arterial wall shear stress (90 dynes/cm2) induces platelet aggregation that is associated with the phosphorylation of pleckstrin, a M(r) 47,000 protein kinase C substrate (p47). Shear-induced p47 phosphorylation depends entirely on vWF binding to platelet glycoprotein (Gp) Ib and GpIIb-IIIa, and the specific inhibition of protein kinase C with the staurosporine analogue Ro 31-7549 inhibits the full aggregation response to shear. Shear stress-induced platelet p47 phosphorylation occurs independent of any measurable change in diacylglycerol mass or hydrolysis of phosphatidylinositol 4,5-bisphosphate. These results indicate that mechanical shear stress induces vWF to bind to platelet GpIb and GpIIb-IIIa, stimulating a diacylglycerol-independent pathway of protein kinase C activation that contributes to platelet aggregation in response to shear.
血管壁处高水平的流体剪切应力直接刺激血管性血友病因子（vWF）介导的血小板黏附和聚集，从而促进动脉血栓形成的发病机制。我们发现，病理性水平的动脉壁剪切应力（90达因/平方厘米）可诱导血小板聚集，这与一种分子量为47,000的蛋白激酶C底物（p47）即普列克底物蛋白的磷酸化有关。剪切诱导的p47磷酸化完全依赖于vWF与血小板糖蛋白（Gp）Ib和GpIIb-IIIa的结合，而用星形孢菌素类似物Ro 31-7549特异性抑制蛋白激酶C可抑制对剪切的完全聚集反应。剪切应力诱导的血小板p47磷酸化的发生与二酰基甘油量或磷脂酰肌醇4,5-二磷酸水解的任何可测量变化无关。这些结果表明，机械剪切应力诱导vWF与血小板GpIb和GpIIb-IIIa结合，刺激蛋白激酶C激活的一条不依赖二酰基甘油的途径，这有助于血小板对剪切的聚集反应。
