Experimental evidence reveals SHIP negatively regulates PKB activation and myeloid cell survival, suggesting implications for myeloid cell hyperplasia.
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.
No takes yet. Share an insight, caveat, or question.
Liu et al. (1999) studied this question.
Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context: