SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt activation and myeloid cell survival
Abstract
SHIP is an inositol 5′ phosphatase that hydrolyzes the PI3′K product PI(3,4,5)P3. We show that SHIP-deficient mice exhibit dramatic chronic hyperplasia of myeloid cells resulting in splenomegaly, lymphadenopathy, and myeloid infiltration of vital organs. Neutrophils and bone marrow-derived mast cells from SHIP−/− mice are less susceptible to programmed cell death induced by various apoptotic stimuli or by growth factor withdrawal. Engagement of IL3-R and GM–CSF-R in these cells leads to increased and prolonged PI3′K-dependent PI(3,4,5)P3 accumulation and PKB activation. These data indicate that SHIP is a negative regulator of growth factor-mediated PKB activation and myeloid cell survival.
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↵Corresponding author.
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E-MAIL Jpenning{at}amgen.com; FAX (416) 204-2278.
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- Received December 4, 1998.
- Accepted February 3, 1999.
- Cold Spring Harbor Laboratory Press