PKC delta survival signaling in cells containing an activated p21 protein requires PDK1

• Published in: Cellular signalling 2009-04, Vol.21 (4), p.502-508
• Main Authors: Xia, Shuhua, Chen, Zhihong, man, Lora W, Faller, Douglas V
• Format: Article
• Language: English
• ISSN: 0898-6568
• DOI: 10.1016/j.cellsig.2008.12.002

Protein kinase C delta (PKC delta ) modulates cell survival and apoptosis in diverse cellular systems. We recently reported that PKC delta functions as a critical anti-apoptotic signal transducer in cells containing activated p21Ras and results in the activation of AKT, thereby promoting cell survival. How PKC delta is regulated by p21Ras, however, remains incompletely understood. In this study, we show that PKC delta , as a transducer of anti-apoptotic signals, is activated by phosphotidylinositol 3' kinase/phosphoinositide-dependent kinase 1 (PI3K-PDK1) to deliver the survival signal to Akt in the environment of activated p21Ras. PDK1 is upregulated in cells containing an activated p21Ras. Knock-down of PDK1, PKC delta , or AKT forces cells containing activated p21Ras to undergo apoptosis. PDK1 regulates PKC delta activity, and constitutive expression of PDK1 increases PKC delta activity in different cell types. Conversely, expression of a kinase-dead (dominant-negative) PDK1 significantly suppresses PKC delta activity. p21Ras-mediated survival signaling is therefore regulated by via a PI3K-AKT pathway, which is dependent upon both PDK1 and PKC delta , and PDK1 activates and regulates PKC delta to determine the fate of cells containing a mutated, activated p21Ras.