SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt activation and myeloid cell survival

AUTOR(ES)

Liu, Qiurong

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

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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