Szamałek Mateusz, Baer-Dubowska Wanda
Katedra Biochemii Farmaceutycznej, Uniwersytet Medyczny im. K. Marcinkowskiego, Poznań.
Postepy Biochem. 2007;53(2):112-20.
The Ras proteins, members of small GTP-binding protein family, are regulated through the exchange of GTP/GDP nucleotide. The activity of the Ras proteins is controlled by guanine nucleotide exchange factors (GEFs) and GTP-ase activating proteins (GAPs), which activate and inactivate G proteins respectively. Beside other, well known Ras-activating GEFs, the new class of such factors was recently described. RasGRP family, known also as CalDAG-GEF, consists of four members. C1 domain, allows them to bind diacylglycerol as well as DAG-analogs like phorbol esters. Binding of the ligand leads to activation of RasGRPs and in consequence to the activation of Ras and Rap proteins by the exchange of bounded guanine nucleotides. The signal transmitted by RasGRP is terminated as a result of DAG phosphorylation catalyzed by diacylglycerol kinase (DGK). Location of RasGRP proteins on the crossing of signaling cascades and broad tissue expression pattern involve them in many events essential for the cell function. RasGRP proteins play roles in such phenomena as: T cells maturation and functioning, B cells response, platelet aggregation, mast cells activity regulation, transformation and many other. In this review, structure and function of RasGRP proteins, as well as their role in neoplastic transformation are described.
Ras蛋白是小GTP结合蛋白家族的成员，通过GTP/GDP核苷酸的交换来调节。Ras蛋白的活性由鸟嘌呤核苷酸交换因子（GEFs）和GTP酶激活蛋白（GAPs）控制，它们分别激活和失活G蛋白。除了其他众所周知的Ras激活GEFs外，最近还描述了这类因子的新类别。RasGRP家族，也称为CalDAG-GEF，由四个成员组成。C1结构域使它们能够结合二酰基甘油以及佛波酯等二酰基甘油类似物。配体的结合导致RasGRP的激活，进而通过结合的鸟嘌呤核苷酸的交换激活Ras和Rap蛋白。由RasGRP传递的信号由于二酰基甘油激酶（DGK）催化的二酰基甘油磷酸化而终止。RasGRP蛋白在信号级联的交叉点的定位和广泛的组织表达模式使其参与许多对细胞功能至关重要的事件。RasGRP蛋白在诸如T细胞成熟和功能、B细胞反应、血小板聚集、肥大细胞活性调节、转化等现象中发挥作用。在这篇综述中，描述了RasGRP蛋白的结构和功能，以及它们在肿瘤转化中的作用。
