SHIP2 (inositol polyphosphate-5 phosphatase-like 1), contains a phosphatase domain and an SH2 (src-homology domain 2) motif. SHIP2 iswidely expressed in fibroblast and nonhematopoietic tumor cell lines. Tyrosine phosphorylation of SHIP2 occurrs in response to treatment of cells with EGF, platelet-derived growth factor (PDGF), nerve growth factor (NGF), insulin-like growth factor-1 (IGF1), or insulin. EGF and PDGF induces transient tyrosine phosphorylation of SHIP2, while treatment of cells with NGF, IGF1, or insulin results in prolonged tyrosine phosphorylation of SHIP2, indicaating that SHIP2 may play a significant role in regulation of phosphatidylinositol 3-prime-kinase signaling by growth factors and insulin. Some animal models indicate that SHIP2 is a potent negative regulator of insulin signaling and insulin sensitivity in vivo, while others suggest that SHIP2 mediates obesity resistance but not changes in glucose and insulin homeostasis.