CLONING AND CHARACTERIZATION OF HUMAN SHIP, THE 145-KD INOSITOL 5-PHOSPHATASE THAT ASSOCIATES WITH SHC AFTER CYTOKINE STIMULATION

We recently cloned and sequenced a cDNA encoding a 145-kD protein from the murine hematopoietic cell line B6SUtA(1) that becomes tyrosine ph osphorylated and associated with She after cytokine stimulation. Based on its domains and enzymatic activity, we named this protein SHIP for SH2-containing inositol phosphatase (Damen et al, Proc Natl Acad Sci USA 93:1689, 1996). We describe here the cloning of the human homologu e of murine SHIP (mSHIP) from a human megakaryocytic cell line (MO7e) lambda gt11 cDNA library using two nonoverlapping mSHIP cDNA fragments as probes. Northern blot analysis suggests that human SHIP (hSHIP) is expressed as a 5.3-kb mRNA in human bone marrow and a wide variety of other tissues. Sequence analysis of this cDNA predicts a protein of 1 188 amino acids exhibiting 87.2% overall sequence identity with mSHIP, Contained within the defined open reading frame is an N-terminal, gro up I src homology 2 (SH2) domain; three NXXY motifs that, if phosphory lated, could be bound by phosphotyrosine binding (PTB) domains; a C-te rminal proline-rich region; and two centrally located inositol polypho sphate 5-phosphatase motifs. Fluorescence in situ hybridization, using the full-length hSHIP cDNA as a probe, mapped hSHIP to the long arm o f chromosome 2 at the border between 2q36 and 2q37. (C) 1996 by The Am erican Society of Hematology.