SHIP, a new player in cytokine-induced signalling

Abstract

We recently purified and cloned the cDNAs for the murine and human forms of a novel 145 kDa inositol polyphosphate 5-phosphatase (5-ptase) that becomes tyrosine phosphorylated and associated with Shc following stimulation of hemopoietic cells with multiple cytokines. Unlike most 5-ptases which hydrolyze phosphatidylinositol-4,5-P₂-bisphosphate (PI-4,5-P₂) and/ or inositol-1,4,5-trisphosphate (I-1,4,5-P₃), this enzyme selectively hydrolyzes the 5′-phosphate from inositol-1,3,4,5-tetraphosphate (I-1,3,4,5-P₄) and phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P₃), two inositol polyphosphates recently implicated in growth factor-mediated signalling. This 5-ptase is also unique among 5-ptases in that it is the only one to date to possess an SH2 domain. In this review we discuss the cloning, the Shc binding and the potential role of this protein, which we call SHIP, for SH 2-containing inositol 5- phosphatase, in cell proliferation, differentiation and apoptosis.