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 translocation 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 cells and the growth of β cells.PHIP1 also induces the activation of PKB which can promote the survival of β cells.The relations of PHIP with the other signal moleculars in INS / IGF signaling pathway are not clear and further experiments work is required.