PDK1: the major transducer of PI 3-kinase actions.
Most of the cellular responses to phosphatidylinositol 3-kinase activation and phosphatidylinositol 3,4,5-trisphosphate production are mediated by the activation of a group of AGC kinases comprising PKB, S6K, RSK, SGK and PKC isoforms, which play essential roles in regulating physiological processes related to cell growth, proliferation, survival and metabolism. All these growth-factor-stimulated AGC kinases possess a common upstream activator, namely PDK1, a master kinase, which, being constitutively active, is still able to phosphorylate and activate its AGC substrates in response to rises in the levels of the PtdIns(3,4,5)P(3) second messenger. In this chapter, the biochemical, structural and genetic data on the mechanism of action and physiological roles of PDK1 are reviewed, and its potential as a pharmaceutical target for the design of drugs therapeutically beneficial to treat human disease such us diabetes and cancer is discussed.
Bayascas
José Ramón
JR
Institut de Neurociències & Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain. joseramon.bayascas@uab.cat
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
D064413:3-Phosphoinositide-Dependent Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; C500984:CRTC1 protein, human; C493245:CRTC2 protein, human; C578562:PDPK1 protein, human