Editorial
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World J Biol Chem. Aug 26, 2010; 1(8): 239-247
Published online Aug 26, 2010. doi: 10.4331/wjbc.v1.i8.239
Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer
Yuwen Li, Keum-Jin Yang, Jongsun Park
Yuwen Li, Keum-Jin Yang, Jongsun Park, Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea
Author contributions: Li Y and Yang KJ contributed equally to this work; Li Y and Yang KJ wrote the paper; Park J edited the paper.
Supported by National Research Foundation of Korea grant funded by the Korea Government (MEST), No. 2010-0001356; and by a grant from the National R and D Program for Cancer Control funded by Ministry of Health and Welfare, Republic of Korea, No. 0720560
Correspondence to: Jongsun Park, PhD, Associate Professor, Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea. insulin@cnu.ac.kr
Telephone: +82-42-5808252 Fax: +82-42-5856627
Received: June 4, 2010
Revised: July 13, 2010
Accepted: July 20, 2010
Published online: August 26, 2010
Abstract

3-phosphoinositide-dependent protein kinase-1 (PDK1) is a central mediator of cellular signaling between phosphoinositide-3 kinase and various intracellular serine/threonine kinases, including protein kinase B, p70 ribosomal S6 kinase, serum and glucocorticoid-inducible kinase, and protein kinase C. PDK1 activates members of the AGC family of protein kinases by phosphorylating serine/threonine residues in the activation loop. Here, we review the regulatory mechanisms of PDK1 and its roles in cancer. PDK1 is activated by autophosphorylation in the activation loop and other serine residues, as well as by phosphorylation of Tyr-9 and Tyr-373/376. Src appears to recognize PDK1 following tyrosine phosphorylation. The role of heat shock protein 90 in regulating PDK1 stability and PDK1-Src complex formation are also discussed. Furthermore, we summarize the subcellular distribution of PDK1. Finally, an important role for PDK1 in cancer chemotherapy is proposed. In conclusion, a better understanding of its molecular regulatory mechanisms in various signaling pathways will help to explain how PDK1 acts as an oncogenic kinase in various cancers, and will contribute to the development of novel cancer chemotherapies.

Keywords: 3-phosphoinositide-dependent protein kinase-1; Protein kinase B; Oncogenic kinase; Cell signaling; Cancer therapy