Open AccessMultiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer
Author(s) -
Yuwen Li,
KeumJin Yang,
Jongsun Park
Publication year - 2010
Publication title -
world journal of biological chemistry
Language(s) - English
Resource type - Journals
ISSN - 1949-8454
DOI - 10.4331/wjbc.v1.i8.239
Subject(s) - ribosomal s6 kinase , map kinase kinase kinase , proto oncogene tyrosine protein kinase src , map2k7 , ask1 , c raf , autophosphorylation , microbiology and biotechnology , mitogen activated protein kinase kinase , cyclin dependent kinase 9 , cancer research , protein kinase a , cyclin dependent kinase 2 , protein phosphorylation , kinase , phosphorylation , p70 s6 kinase 1 , biology , protein kinase b
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.