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PMID: 22992589 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Assembly of allosteric macromolecular switches: lessons from PKA.

Nature reviews. Molecular cell biology ·Vol. 13 ·No. 10 ·2012-10-00 ·Pages 646-58

Taylor SS, Ilouz R, Zhang P, Kornev AP

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.

MeSH Terms
Catalytic Domain Crystallography, X-Ray Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/chemistry,metabolism Macromolecular Substances/chemistry,metabolism Phosphorylation Protein Isoforms Protein Structure, Tertiary Signal Transduction
Chemicals
Macromolecular Substances Protein Isoforms Cyclic AMP Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Taylor Susan S
Department of Pharmacology, University of California, San Diego, La Jolla, 92093-90654, USA. [email protected]
Ilouz Ronit
Zhang Ping
Kornev Alexandr P
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Article Info
Journal
Nature reviews. Molecular cell biology
Abbr.
Nat Rev Mol Cell Biol
ISSN
1471-0080
DOI
10.1038/nrm3432
Email
[email protected]
Published
2012-10-00
Epub
2012-00-20
Pages
646-58
Language
English
Region
England
NLM ID
100962782
PMCID
PMC3985763
Subset
IM
Grants
NIGMS NIH HHS · GM34921 · United States
NIDDK NIH HHS · P01 DK054441 · United States
NIDDK NIH HHS · DK54441 · United States
NIGMS NIH HHS · R01 GM019301 · United States
NIGMS NIH HHS · R01 GM034921 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R37 GM019301 · United States
NIGMS NIH HHS · GM19301 · United States
External Links
PubMed source DOI: 10.1038/nrm3432 PMC Full Text View journal details
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