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Molecular and Cellular Biology, February 2004, p. 1493-1504, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1493-1504.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Regulation of Apoptosis by the Ft1 Protein, a New Modulator of Protein Kinase B/Akt

Département de Biochimie, Université de Montréal, Succursale centre-ville, Montréal, Québec H3C 3J7, Canada

Received 31 March 2003/ Returned for modification 20 June 2003/ Accepted 19 November 2003

The serine/threonine kinase protein kinase B (PKB)/Akt plays a central role in many cellular processes, including cell growth, glucose metabolism, and apoptosis. However, the identification and validation of novel regulators or effectors is key to future advances in understanding the multiple functions of PKB. Here we report the identification of a novel PKB binding protein, called Ft1, from a cDNA library screen using a green fluorescent protein-based protein-fragment complementation assay. We show that the Ft1 protein interacts directly with PKB, enhancing the phosphorylation of both of its regulatory sites by promoting its interaction with the upstream kinase PDK1. Further, the modulation of PKB activity by Ft1 has a strong effect on the apoptosis susceptibility of T lymphocytes treated with glucocorticoids. We demonstrate that this phenomenon occurs via a PDK1/PKB/GSK3/NF-ATc signaling cascade that controls the production of the proapoptotic hormone Fas ligand. The wide distribution of Ft1 in adult tissues suggests that it could be a general regulator of PKB activity in the control of differentiation, proliferation, and apoptosis in many cell types.

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