Assembly of allosteric macromolecular switches: lessons from PKA

Nat Rev Mol Cell Biol. 2012 Oct;13(10):646-58. doi: 10.1038/nrm3432. Epub 2012 Sep 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / chemistry*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / metabolism*
  • Phosphorylation
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Signal Transduction

Substances

  • Macromolecular Substances
  • Protein Isoforms
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases