Aix Marseille University, INSERM, INRAE, C2VN, 13005 Marseille, France.
Hematology Laboratory, APHM, CHU Timone, 13005 Marseille, France.
Int J Mol Sci. 2020 Feb 6;21(3):1075. doi: 10.3390/ijms21031075.
RasGRP2 is calcium and diacylglycerol-regulated guanine nucleotide exchange factor I that activates Rap1, which is an essential signaling-knot in "inside-out" αIIbβ3 integrin activation in platelets. Inherited platelet function disorder caused by variants of RASGRP2 represents a new congenital bleeding disorder referred to as platelet-type bleeding disorder-18 (BDPLT18). We review here the structure of RasGRP2 and its functions in the pathophysiology of platelets and of the other cellular types that express it. We will also examine the different pathogenic variants reported so far as well as strategies for the diagnosis and management of patients with BDPLT18.
RasGRP2 是钙和二酰基甘油调节的鸟嘌呤核苷酸交换因子 I,可激活 Rap1,这是血小板中“内-外”αIIbβ3 整合素激活的关键信号节点。由 RasGRP2 变异引起的遗传性血小板功能障碍代表了一种新的先天性出血性疾病,称为血小板型出血障碍 18 型(BDPLT18)。我们在此回顾 RasGRP2 的结构及其在血小板和表达它的其他细胞类型的病理生理学中的功能。我们还将检查迄今为止报道的不同致病性变异体以及诊断和管理 BDPLT18 患者的策略。