SH2域
鸟嘌呤核苷酸交换因子
罗亚
生物
生物化学
GTP酶
原癌基因酪氨酸蛋白激酶Src
化学
磷酸化
信号转导
作者
Bo Wu,Fengsong Wang,Jiahai Zhang,Zhiyong Zhang,Liying Qin,Junhui Peng,Fudong Li,Jianping Liu,Guowei Lü,Qingguo Gong,Xuebiao Yao,Jihui Wu,Yunyu Shi
标识
DOI:10.1016/j.jsb.2012.06.011
摘要
Vav2 is a ubiquitous guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. It regulates processes including cell migration, neuronal development and phagocytosis through interactions with different proteins. In this study, Arap3, a dual GTPase-activating protein (GAP) for RhoA and Arf6, was first identified to be a novel interaction partner for Vav2 both in vitro and in vivo. ITC and NMR chemical shift perturbation experiments demonstrated that Vav2 SH2 domain was able to interact directly with phosphorylated Y1403 and Y1408 within the C-terminal region of Arap3 with high affinities, with the dissociation constants (Kd) of ≈ 0.27 and ≈ 1.40 μM, respectively. In addition, using different phosphotyrosine peptides, the pY +3 specificity of Vav2 SH2 domain was discovered. The solution structures of Vav2 SH2 domain in free and in complex with the phosphotyrosine peptide pY1408 were therefore determined to understand the structural basis of this recognition specificity. Structural analysis revealed that the presence of a Phe residue in the BG loop (BG6) leads to the formation of a shallow hydrophobic pY +3 pocket on the surface of Vav2 SH2 domain, which determines the pY +3 specificity of Vav2 SH2 domain.
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