Allosteric regulation of GRB2 modulates RAS activation.

Q2 Biochemistry, Genetics and Molecular Biology Small GTPases Pub Date : 2022-01-01 DOI:10.1080/21541248.2022.2089001
Neda S Kazemein Jasemi, Mohammad R Ahmadian
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引用次数: 1

Abstract

RAS activation is a multiple-step process in which linkage of the extracellular stimuli to the RAS activator SOS1 is the main step in RAS activation. GRB2 adaptor protein is the main modulator in SOS1 recruitment to the plasma membrane and its activation. This interaction is well studied but the exact mechanism of GRB2-SOS1 complex formation and SOS1 activation has yet remained obscure. Here, a new allosteric mechanism for the GRB2 regulation is described as a prerequisite for the modulation of SOS1 activation. This regulatory mechanism comprises a series of intramolecular interactions which are potentiated by GRB2 interaction with upstream ligands.Abbreviations: GRB2, growth factor receptor-bound protein 2; SOS1, son of sevenless 1; RAS, Rat Sarcoma; GEF, guanine nucleotide exchange factor; GAP, GTPase-activating protein; HER2, human epidermal growth factor receptor; SH3, SRC Homology 3; SH2, SRC Homology 2; PRD, proline-rich domain; PRM, proline-rich motif; PRP, proline-rich peptide; RTK, receptor tyrosine kinases.

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GRB2的变构调控可调节RAS的激活。
RAS激活是一个多步骤的过程,其中细胞外刺激与RAS激活子SOS1的连接是RAS激活的主要步骤。GRB2接头蛋白是SOS1向质膜募集和激活的主要调节剂。这种相互作用已经得到了很好的研究,但GRB2-SOS1复合物形成和SOS1激活的确切机制尚不清楚。在这里,GRB2调控的一种新的变构机制被描述为SOS1激活调节的先决条件。这种调控机制包括一系列分子内相互作用,GRB2与上游配体的相互作用增强了这些相互作用。缩写:GRB2,生长因子受体结合蛋白2;SOS1,七少之子1;RAS,大鼠肉瘤;鸟嘌呤核苷酸交换因子;gtpase激活蛋白;HER2,人表皮生长因子受体;SH3, SRC同源3;SH2, SRC同源性2;PRD,脯氨酸富域;PRM,富含脯氨酸的基序;PRP,富含脯氨酸的肽;RTK,受体酪氨酸激酶。
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来源期刊
Small GTPases
Small GTPases Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
6.10
自引率
0.00%
发文量
6
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