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
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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. / Horn, S; Meyer, J; Heukeshoven, J; Fehse, B; Schulze, C; Li, S; Frey, J; Poll, S; Stocking, C; Jücker, M.
In: LEUKEMIA, Vol. 15, No. 1, 01.2001, p. 112-20.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - 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
AU - Horn, S
AU - Meyer, J
AU - Heukeshoven, J
AU - Fehse, B
AU - Schulze, C
AU - Li, S
AU - Frey, J
AU - Poll, S
AU - Stocking, C
AU - Jücker, M
PY - 2001/1
Y1 - 2001/1
N2 - 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.
AB - 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.
KW - Alternative Splicing
KW - Amino Acid Sequence
KW - Blood Cells/enzymology
KW - Bone Marrow Cells/enzymology
KW - Carboxylic Acids
KW - Cells, Cultured
KW - Humans
KW - Isoenzymes/metabolism
KW - Molecular Sequence Data
KW - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
KW - Phosphoric Monoester Hydrolases/metabolism
U2 - 10.1038/sj.leu.2401990
DO - 10.1038/sj.leu.2401990
M3 - SCORING: Journal article
C2 - 11243378
VL - 15
SP - 112
EP - 120
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 1
ER -
