胰岛素受体底物PH结构域相互作用蛋白结构和功能研究进展

PHIP是一种与胰腺β细胞中胰岛素受体底物（IRS）的PH结构域相互作用的蛋白。根据小鼠PHIP（mPHIP）mRNA翻译的不同起始位点,除全长的PHIP1外,mPHIP基因还编码其他3种不同变异体。在胰岛素诱导的信号途径中,主要分布于细胞核的PHIP1和IRS-1的PH结构域相互作用,介导IRS蛋白酪氨酸的磷酸化。IRS-2和PHIP1的共表达能诱导IRS在细胞膜上的定位,促进葡萄糖转运蛋白4（GLUT4）向细胞质膜的转移。PHIP1的表达能提高β-细胞内细胞周期蛋白D2的表达,促进β细胞的生长。PHIP1的表达活化蛋白激酶B（PKB）,活化的PKB能明显抑制β细胞的凋亡。PHIP与胰岛素信号传导途径中其他信号分子的相互作用机制尚不明确。

Progress in the Studies on Structure and Function of Pleckstrin Homology Domain-Interacting Protein for Insulin Receptor Substrate

Pleckstrin homology domain-interacting protein（PHIP） is the protein that interacts with the pleckstrin homology （PH） domain of the insulin receptor substrate（IRS） in β cells of pancreas. With multiple translation initiation start sites of mPHIP, mPHIP genes encode the other three kinds of PHIP, except the full length of PHIP1. In the nucleus of β cells, PHIP1 binds to the PH domain of IRS-1, which can induce the tyrosine phosphorylation of IRS protein through insulin/ insulin-like growth factor signaling pathway. The co-expression of PHIP1 and IRS-2 can induced the localiztion to the membrane of IRS-2 and the transloeation of glucose transproter 4 （GLUT4） from intracellular compartments to the plasma membrane. The expression of PHIP1 can improve the indensity of cyclin D2 in β ceils and the growth of β cells. PHIP1 also induces the activation of PKB which can promote the survival of β cells. The relations of PH1P with the other signal moleculars in INS/IGF signaling pathway are not clear and further experiments work is required.