Review

Oncogene (2003) 22, 8983–8998. doi:10.1038/sj.onc.1207115

PI3K/Akt and apoptosis: size matters

Thomas F Franke1, Christoph P Hornik1, Lisa Segev1, Grigoriy A Shostak1 and Chizuru Sugimoto1

1Department of Pharmacology, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, PH7-W318, New York, NY 10032, USA

Correspondence: TF Franke, Fax: 212-342-1921; E-mail: tff5@columbia.edu

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Abstract

Recent research has examined Akt and Akt-related serine–threonine kinases in signaling cascades that regulate cell survival and are important in the pathogenesis of degenerative diseases and in cancer. We seek to recapitulate the research that has helped to define the current understanding of the role of the Akt pathway under normal and pathologic conditions, also in view of genetic models of Akt function. In particular, we will evaluate the mechanisms of Akt regulation and the role of Akt substrates in Akt-dependent biologic responses in the decisions of cell death and cell survival. Here, we hope to establish the mechanisms of apoptosis suppression by Akt kinase as a framework for a more general understanding of growth factor-dependent regulation of cell survival.

Keywords:

Akt, PI3K, PTEN, PDK2, apoptosis, genetic models

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