SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt activation and myeloid cell survival
SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt activation and myeloid cell survival
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DOI：
10.1101/gad.13.7.786
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发表时间：
1999-04-01
影响因子：
10.5
通讯作者：
Penninger, JM
中科院分区：
文献类型：
--
作者：
Liu, QR;Sasaki, T;Penninger, JM
SHIP是一种肌醇5‘磷酸酶，能降解PI3’K产物PI(3，4，5)P-3。我们发现SHIP缺陷小鼠表现出严重的慢性髓系细胞增生，导致脾肿大、淋巴结病和重要器官的髓样浸润。SHIP-/-小鼠的中性粒细胞和骨髓来源的肥大细胞不太容易受到各种凋亡刺激或生长因子停用引起的程序性细胞死亡的影响。IL-3-R和GM-CSF-R在这些细胞中的结合导致依赖PI3‘K的PI(3，4，5)P-3积聚和PKB激活增加和延长。这些数据表明SHIP是生长因子介导的PKB激活和髓系细胞存活的负调控因子。
SHIP is an inositol 5 ' phosphatase that hydrolyzes the PI3 ' K product PI(3,4,5)P-3. 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)P-3 accumulation and PKB activation. These data indicate that SHIP is a negative regulator of growth factor-mediated PKB activation and myeloid cell survival.