Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer

• 作者: Jongsun Park Keum-Jin Yang
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: 3-phosphoinositide-dependent PROTEIN kinase-1 PROTEIN KINASE B Oncogenic KINASE Cell SIGNALING Cancer therapy
• 年，卷（期）: 2010,（8）
• 页码范围: 239-247
• 页数: 9页
• 分类号: R730.2

摘要

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.