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Publication : Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt.

First Author  Remy I Year  2004
Journal  Mol Cell Biol Volume  24
Issue  4 Pages  1493-504
PubMed ID  14749367 Mgi Jnum  J:87682
Mgi Id  MGI:3027417 Doi  10.1128/MCB.24.4.1493-1504.2004
Citation  Remy I, et al. (2004) Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt. Mol Cell Biol 24(4):1493-504
abstractText  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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