Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt.
نویسندگان
چکیده
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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Kashiri M1, Safa M2, Kazemi A3 1Dept. of Hematology, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran 2Cellular and Molecular Research Center, Dept. of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran 3Dept. of Hematology & Blood Banking, School of Allied Medicine, Iran University of Medical Sciences, Tehran, I...
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ورودعنوان ژورنال:
- Molecular and cellular biology
دوره 24 4 شماره
صفحات -
تاریخ انتشار 2004