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 negative signalling in B cells and mast cells and in the down-regulation of cytokine 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 splicing. Additional smaller forms of SHIP which are truncated at the carboxy terminus have been described in bone marrow and peripheral blood mononuclear cells (PBMC). Our data demonstrate that human bone marrow cells and PBMC from healthy donors and patients with acute myeloid leukemia express the 145 kDa form of SHIP and low amounts of a 135 kDa form of SHIP in vivo whereas C-terminal-truncated SHIP proteins are generated by a PMSF-sensitive protease during the preparation of cell lysates in vitro. We have further characterized this protease and identified a proteolytic cleavage site in the human 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 and peripheral blood cells from normal donors and patients with acute myeloid leukemia.
Institut für Medizinische Biochemie und Molekularbiologie, Abteilung für Zelluläre Signaltransduktion, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Germany.
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S
Horn
J
J
Meyer
J
J
Heukeshoven
B
B
Fehse
C
C
Schulze
S
S
Li
J
J
Frey
S
S
Poll
C
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Stocking
M
M
Jücker
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001773:Blood Cells / Q000201:enzymology*; D001854:Bone Marrow Cells / Q000201:enzymology*; D002264:Carboxylic Acids; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*
D002264:Carboxylic Acids; D007527:Isoenzymes; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases