Acute regulation of PDK1 by a complex interplay of molecular switches

被引：27

作者：

Calleja, Veronique ^{[1
,2
]}

Laguerre, Michel ^{[3
]}

de las Heras-Martinez, Gloria ^{[4
]}

Parker, Peter J. ^{[2
,5
]}

Requejo-Isidro, Jose ^{[4
]}

Larijani, Banafshe ^{[1
,6
,7
]}

机构：

[1] Canc Res UK London Res Inst, Cell Biophys Lab, London WC2A 3LY, England

[2] Canc Res UK London Res Inst, Prot Phosphorylat Lab, London WC2A 3LY, England

[3] Univ Bordeaux, Inst Europeen Chim & Biol, UMR 5248, F-33607 Pessac, France

[4] Univ Basque Country, CSIC, Unidad Biofis, Biophoton Lab, Leioa 48940, Spain

[5] Kings Coll London, Div Canc Studies, London SE1 1UL, England

[6] Ikerbasque, Basque Fdn Sci, Cell Biophys Lab, Bilbao 48011, Spain

[7] Univ Basque Country, CSIC, Unidad Biofis, Leioa 48940, Spain

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2014年 / 42卷

关键词：

activation dynamics; homodimerization; phosphoinositide-dependent kinase 1 (PDK1); phosphorylation; subcellular localization; 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1; PHOSPHOINOSITIDE-DEPENDENT KINASE-1; PLASMA-MEMBRANE MICRODOMAINS; TYROSINE PHOSPHORYLATION; IN-VIVO; NUCLEAR TRANSLOCATION; NEGATIVE REGULATION; CATALYTIC-ACTIVITY; PH DOMAIN; ACTIVATION;

D O I：

10.1042/BST20140222

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phosphoinositide-dependent kinase 1 (PDK1) is the master regulator of at least 23 other AGC kinases whose downstream signalling has often been implicated in various diseases and in particular in cancer. Therefore there has been great interest in determining how PDK1 is controlled and how it regulates its substrates spatially and temporally. The understanding of these mechanisms could offer new possibilities for therapeutic intervention. Over the years, a more comprehensive view of the mechanisms involved in the regulation of PDK1 has emerged and these comprise serine/threonine as well as tyrosine phosphorylation, subcellular localization, regulator binding and conformation status. In the present review, we discuss how various molecular mechanisms are together responsible for the conformational regulation behind the activation of PDK1 in cells.

引用

页码：1435 / 1440

页数：6

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