Dissecting the role of the 3-phosphoinositide-dependent protein kinase-1 (PDK1) signalling pathways

Research output: Contribution to journalReview articleResearchpeer-review

74 Citations (Scopus)

Abstract

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)P3] 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. ©2008 Landes Bioscience.
Original languageEnglish
Pages (from-to)2978-2982
JournalCell Cycle
Volume7
Issue number19
DOIs
Publication statusPublished - 1 Oct 2008

Keywords

  • Diabetes
  • Hyperinsulinemia
  • Knock-in mice
  • PDK1
  • PKB/Akt

Fingerprint

Dive into the research topics of 'Dissecting the role of the 3-phosphoinositide-dependent protein kinase-1 (PDK1) signalling pathways'. Together they form a unique fingerprint.

Cite this