The inositol 5-phosphatase SHIP is expressed as 145 and 135 kDa proteins in blood and bone marrow cells in vivo, whereas carboxyl-truncated forms of SHIP are generated by proteolytic cleavage in vitro

The inositol polyphosphate 5-phosphatase SHIP plays an important role in ne gative signalling in B cells and mast cells and in the down-regulation of c ytokine receptor-mediated signals in myeloid cells. SHIP is expressed as a 145 kDa full-length protein and an isoform of 135 kDa due to alternative sp licing. Additional smaller forms of SHIP which are truncated at the carboxy terminus have been described in bone marrow and peripheral blood mononucle ar cells (PBMC). Our data demonstrate that human bone marrow cells and PBMC from healthy donors and patients with acute myeloid leukemia express the 1 45 kDa form of SHIP and low amounts of a 135 kDa form of SHIP in vivo where as C-terminal-truncated SHIP proteins are generated by a PMSF-sensitive pro tease during the preparation of cell lysates in vitro. We have further char acterized this protease and identified a proteolytic cleavage site in the h uman SHIP protein C-terminal to tryptophan residue 941. These data support a physiological role for the 145 and 135 kDa forms of SHIP in bone marrow a nd peripheral blood cells from normal donors and patients with acute myeloi d leukemia.