Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA.
George W. Woodruff School of Mechanical Engineering.
Platelets. 2022 Aug 18;33(6):823-832. doi: 10.1080/09537104.2022.2071852. Epub 2022 May 26.
The glycoprotein Ib-IX (GPIb-IX) complex mediates initial platelet adhesion to von Willebrand factor (VWF) immobilized on subendothelial matrix and endothelial surfaces, and transmits VWF binding-induced signals to stimulate platelet activation. GPIb-IX also functions as part of a mechanosensor to convert mechanical force received via VWF binding into intracellular signals, thereby greatly enhancing platelet activation. Thrombin binding to GPIb-IX initiates GPIb-IX signaling cooperatively with protease-activated receptors to synergistically stimulate the platelet response to low-dose thrombin. GPIb-IX signaling may also occur following the binding of other GPIb-IX ligands such as leukocyte integrin αβ and red cell-derived semaphorin 7A, contributing to thrombo-inflammation. GPIb-IX signaling requires the interaction between the cytoplasmic domains of GPIb-IX and 14-3-3 protein and is mediated through Src family kinases, the Rho family of small GTPases, phosphoinositide 3-kinase-Akt-cGMP-mitogen-activated protein kinase, and LIM kinase 1 signaling pathways, leading to calcium mobilization, integrin activation, and granule secretion. This review summarizes the current understanding of GPIb-IX signaling.
糖蛋白 Ib-IX（GPIb-IX）复合物介导血小板最初与固定在血管内皮基质和表面上的血管性血友病因子（VWF）的黏附，并传递 VWF 结合诱导的信号以刺激血小板激活。GPIb-IX 还作为机械感受器的一部分，将通过 VWF 结合接收的机械力转化为细胞内信号，从而大大增强血小板激活。凝血酶与 GPIb-IX 的结合与蛋白酶激活受体协同启动 GPIb-IX 信号，协同刺激血小板对低剂量凝血酶的反应。GPIb-IX 信号也可能发生在其他 GPIb-IX 配体（如白细胞整合素αβ和红细胞衍生的 semaphorin 7A）结合后，导致血栓炎症。GPIb-IX 信号需要 GPIb-IX 和 14-3-3 蛋白的细胞质结构域之间的相互作用，并通过 Src 家族激酶、Rho 家族的小 GTP 酶、磷酸肌醇 3-激酶-Akt-cGMP-有丝分裂原激活蛋白激酶和 LIM 激酶 1 信号通路进行介导，导致钙动员、整合素激活和颗粒分泌。本综述总结了目前对 GPIb-IX 信号的理解。
