title: Acute regulation of PDK1 by a complex interplay of molecular switches.
abstract: 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.
authors.forename: Veronique
authors.initials: V
authors.lastname: Calleja
authors.affiliation: ‡Institut Européen de Chimie et Biologie, Université de Bordeaux, UMR 5248, 2 rue Robert Escarpit, F-33607 Pessac, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Laguerre
authors.affiliation: §Biophotonics Lab, Unidad de Biofísica CSIC-UPV/EHU, Barrio de Sarriena s/n, 48940 Leioa, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: de Las Heras-Martinez
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
authors.affiliation: §Biophotonics Lab, Unidad de Biofísica CSIC-UPV/EHU, Barrio de Sarriena s/n, 48940 Leioa, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Requejo-Isidro
authors.forename: Banafshé
authors.initials: B
authors.lastname: Larijani
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D019281:Dimerization; D004789:Enzyme Activation; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D008024:Ligands; D009363:Neoplasm Proteins; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human