THE 145-KDA PROTEIN-INDUCED TO ASSOCIATE WITH SHC BY MULTIPLE CYTOKINES IS AN INOSITOL TETRAPHOSPHATE AND PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE 5-PHOSPHATASE

A 145-kDa tyrosine-phosphorylated protein that becomes associated with She in response to multiple cytokines has been purified from the muri ne hemopoietic cell line B6SUtA(1). Amino acid sequence data were used to clone the cDNA encoding this protein from a B6SUtA(1) library. The predicted amino acid sequence encodes a unique protein containing an N-terminal src homology 2 domain, two consensus sequences that are tar gets for phosphotyrosine binding domains, a proline-rich region, and t wo motifs highly conserved among inositol polyphosphate 5-phosphatases . Cell lysates immunoprecipitated with antiserum to this protein exhib ited both phosphatidylinositol 3,4,5-trisphosphate and inositol 1,3,4, 5-tetrakisphosphate polyphosphate 5-phosphatase activity. This novel s ignal transduction intermediate may serve to modulate both Ras and ino sitol signaling pathways. Based on its properties, we suggest the 145- kDa protein be called SHIP for SH2-containing inositol phosphatase.