Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway
作者： Asim Khwaja , Pablo Rodriguez‐Viciana , Stefan Wennström , Patricia H Warne , Julian Downward
关键词: mTORC2 、 Kinase 、 Akt/PKB signaling pathway 、 Signal transduction 、 AKT1 、 Anoikis 、 Mitogen-activated protein kinase 、 Cell biology 、 Protein kinase B 、 Biology
摘要: Upon detachment from the extracellular matrix, epithelial cells enter into programmed cell death, a phenomenon known as anoikis, ensuring that they are unable to survive in an inappropriate location. Activated ras oncogenes protect this form of apoptosis. The nature survival signals activated by integrin engagement and usurped oncogenic Ras unknown: here we show both cases phosphoinositide 3-OH kinase (PI 3-kinase), but not Raf, mediates protection, acting through protein B/Akt (PKB/Akt). Constitutively PI 3-kinase or PKB/Akt block while inhibition abrogates protection Ras, PKB/Akt. Inhibition either induces apoptosis adherent cells. Attachment matrix leads rapid elevation levels lipid products activity, which remain high Ras-transformed even suspension. is therefore implicated key mediator aberrant absence attachment, matrix-induced normal
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