Premium
Regulation of cell survival by CIB1, a new modulator of phosphoinositide‐dependent protein kinase‐1 (PDK1)
Author(s) -
Zhao Bin,
Leisner Tina M,
McFadden Andrew W,
Parise Leslie V
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb12-d
Subject(s) - microbiology and biotechnology , chemistry , cell growth , kinase , protein kinase a , apoptosis , pi3k/akt/mtor pathway , protein kinase b , cancer research , phosphorylation , signal transduction , biology , biochemistry
Regulation of cell survival by CIB1, a new modulator of phosphoinositide‐dependent protein kinase‐1 (PDK1) Our previous findings showed that CIB1‐/‐ MEFs proliferate at a significantly slower rate than wild‐type MEFs, indicating a role for CIB1 in regulating cell growth and survival. To delineate CIB1 downstream signals that contribute to its biological functions, we identified a new CIB1 binding partner, PDK1, by scansite ( www.scansite.mit.edu ). PDK1 activates the AGC protein kinase family and plays an important role in regulating cell growth, survival, and cell cycle progression, but the regulation of PDK1 itself in cells is less clear. Here we demonstrate a direct interaction between CIB1 and PDK1 that further activates PDK1. Furthermore, upon cell adhesion to fibronectin, CIB1 and PDK1 colocalize at the plasma and perinuclear membranes. However, expression of either a non‐myristoylated CIB1 (G2A) mutant or a mutant with a diminished binding to PDK1 [CIB1 (4A)] resulted in the redistribution of PDK1 to the cytosol, suggesting that CIB1 regulates PDK1 localization in cells. In addition, CIB1 depletion enhanced apoptosis in response to apoptotic stimuli, and this response was partially overcome by PDK1 overexpression. Importantly, overexpression of either CIB1 (G2A) or CIB1 (4A) lacked protection against cell death in response to apoptotic stimuli compared to wild‐type CIB1. In conclusion, these results demonstrate that CIB1 is a critical regulator of cell survival, in part via a PDK1 signaling pathway.