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PMID: 10698680 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The PI3K-PDK1 connection: more than just a road to PKB.

The Biochemical journal ·Vol. 346 Pt 3 ·2000-03-15 ·Pages 561-76

Vanhaesebroeck B, Alessi DR

Abstract

Phosphoinositide 3-kinases (PI3Ks) generate specific inositol lipids that have been implicated in the regulation of cell growth, proliferation, survival, differentiation and cytoskeletal changes. One of the best characterized targets of PI3K lipid products is the protein kinase Akt or protein kinase B (PKB). In quiescent cells, PKB resides in the cytosol in a low-activity conformation. Upon cellular stimulation, PKB is activated through recruitment to cellular membranes by PI3K lipid products and phosphorylation by 3'-phosphoinositide-dependent kinase-1 (PDK1). Here we review the mechanism by which PKB is activated and the downstream actions of this multifunctional kinase. We also discuss the evidence that PDK1 may be involved in the activation of protein kinases other than PKB, the mechanisms by which this activity of PDK1 could be regulated and the possibility that some of the currently postulated PKB substrates targets might in fact be phosphorylated by PDK1-regulated kinases other than PKB.

MeSH Terms
3-Phosphoinositide-Dependent Protein Kinases Amino Acid Sequence Animals Binding Sites Enzyme Activation Humans Phosphatidylinositol 3-Kinases/metabolism Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins/chemistry,metabolism Proto-Oncogene Proteins c-akt Sequence Homology, Amino Acid Signal Transduction
Chemicals
Proto-Oncogene Proteins 3-Phosphoinositide-Dependent Protein Kinases AKT1 protein, human PDPK1 protein, human Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Vanhaesebroeck B
Cell Signalling Group, Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, U.K. [email protected]
Alessi D R
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Email
[email protected]
Published
2000-03-15
Pages
561-76
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1220886
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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