The Activation of Protein Kinase A by the Calcium-Binding Protein S100A1 Is Independent of Cyclic AMP

Biochemistry. 2017 May 2;56(17):2328-2337. doi: 10.1021/acs.biochem.7b00117. Epub 2017 Apr 18.

Abstract

Biochemical and structural studies demonstrate that S100A1 is involved in a Ca2+-dependent interaction with the type 2α and type 2β regulatory subunits of protein kinase A (PKA) (RIIα and RIIβ) to activate holo-PKA. The interaction was specific for S100A1 because other calcium-binding proteins (i.e., S100B and calmodulin) had no effect. Likewise, a role for S100A1 in PKA-dependent signaling was established because the PKA-dependent subcellular redistribution of HDAC4 was abolished in cells derived from S100A1 knockout mice. Thus, the Ca2+-dependent interaction between S100A1 and the type 2 regulatory subunits represents a novel mechanism that provides a link between Ca2+ and PKA signaling, which is important for the regulation of gene expression in skeletal muscle via HDAC4 cytosolic-nuclear trafficking.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Calcium Signaling*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / genetics
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / metabolism*
  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / genetics
  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / metabolism*
  • Enzyme Activation
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / metabolism*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / metabolism
  • S100 Proteins / genetics
  • S100 Proteins / metabolism*

Substances

  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit
  • Prkar2a protein, mouse
  • Prkar2b protein, mouse
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • S100 Proteins
  • S100A1 protein
  • Green Fluorescent Proteins
  • Hdac5 protein, mouse
  • Histone Deacetylases