title: Assembly of allosteric macromolecular switches: lessons from PKA.
abstract: Protein kinases are dynamic molecular switches that have evolved to be only transiently activated. Kinase activity is embedded within a conserved kinase core, which is typically regulated by associated domains, linkers and interacting proteins. Moreover, protein kinases are often tethered to large macromolecular complexes to provide tighter spatiotemporal control. Thus, structural characterization of kinase domains alone is insufficient to explain protein kinase function and regulation in vivo. Recent progress in structural characterization of cyclic AMP-dependent protein kinase (PKA) exemplifies how our knowledge of kinase signalling has evolved by shifting the focus of structural studies from single kinase subunits to macromolecular complexes.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, 92093-90654, USA. staylor@ucsd.edu
authors.forename: Susan S
authors.initials: SS
authors.lastname: Taylor
authors.forename: Ronit
authors.initials: R
authors.lastname: Ilouz
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Alexandr P
authors.initials: AP
authors.lastname: Kornev
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D046911:Macromolecular Substances; D020033:Protein Isoforms; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases