Journal
CELL CYCLE
Volume 7, Issue 19, Pages 2978-2982Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.7.19.6810
Keywords
PDK1; knock-in mice; PKB/Akt; hyperinsulinemia; diabetes
Categories
Funding
- Association for International Cancer Research
- Medical Research Council
- Moffat Charitable Trust
- AstraZeneca
- Boehringer-Ingelheim
- GlaxoSmithKline
- Merck Co., Inc.
- Merck KGaA
- Pfizer
- Spanish Ramon y Cajal Program
- Spanish Government Ministerio de Sanidad y Consumo [PI070101]
- Diabetes UK
Ask authors/readers for more resources
The 3-phosphoinositide-dependent protein kinase-1 (PDK1) mediates the cellular effect of insulin and growth factors by activating a group of kinases including PKB/Akt, S6K, RSK, SGK and PKC isoforms. PDK1 possesses two regulatory domains namely a Pleckstrin Homology (PH) domain that binds to the phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P-3] second messenger, and a substrate binding site termed the PIF-pocket. Employing a combination of biochemical, structural and mouse knock-in approaches we have been able to define the roles that the regulatory domains on PDK1 play. We have established that binding of PDK1 to PtdIns(3,4,5) P3 is essential for efficient activation of PKB isoforms as well as for maintaining normal cell size and insulin sensitivity. In contrast, the PIF-substrate binding pocket of PDK1 is not required for PKB activation, but is necessary for PDK1 to activate all of its other substrates.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available