Regulation of PI(3)K/Akt signalling and cellular transformation by inositol polyphosphate 4‐phosphatase‐1
作者： Ivan Ivetac , Rajendra Gurung , Sandra Hakim , Kristy A Horan , David A Sheffield
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摘要: Akt is a crucial phosphoinositide 3-kinase (PI(3)K) effector that regulates cell proliferation and survival. PI(3)K-generated signals, PtdIns(3,4,5)P3 PtdIns(3,4)P2, direct plasma membrane engagement. Pathological association promotes oncogenesis. PtdIns(3,4)P2 degraded by inositol polyphosphate 4-phosphatase-1 (4-ptase-1) forming PtdIns(3)P; however, the role of 4-ptase-1 in regulating activation function unclear. In mouse embryonic fibroblasts lacking (−/−MEFs), Akt-pleckstrin homology (PH) domain was constitutively membrane-associated both serum-starved agonist-stimulated cells, contrast to +/+MEFs, which it detected only at following serum stimulation. Epidermal growth factor (EGF) stimulation resulted increased Ser473 Thr308-Akt phosphorylation Akt-dependent signalling −/−MEFs, relative +/+MEFs. Significantly, loss decreased apoptosis. SV40-transformed −/−MEFs showed anchorage-independent formed tumours nude mice. This study provides first evidence, our knowledge, controls thereby proliferation, survival tumorigenesis.
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