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

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TitleThe Activation of Protein Kinase A by the Calcium-Binding Protein S100A1 Is Independent of Cyclic AMP.
Publication TypeJournal Article
Year of Publication2017
AuthorsMelville, Z, Hernández-Ochoa, EO, Pratt, SJP, Liu, Y, Pierce, AD, Wilder, PT, Adipietro, KA, Breysse, DH, Varney, KM, Schneider, MF, Weber, DJ
Date Published2017 05 02
KeywordsActive Transport, Cell Nucleus, Animals, Calcium Signaling, Cells, Cultured, Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit, Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit, Enzyme Activation, Green Fluorescent Proteins, Histone Deacetylases, Humans, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Muscle Fibers, Skeletal, Protein Subunits, Rats, Recombinant Fusion Proteins, Recombinant Proteins, S100 Proteins

Biochemical and structural studies demonstrate that S100A1 is involved in a Ca-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 Ca-dependent interaction between S100A1 and the type 2 regulatory subunits represents a novel mechanism that provides a link between Ca and PKA signaling, which is important for the regulation of gene expression in skeletal muscle via HDAC4 cytosolic-nuclear trafficking.

Alternate JournalBiochemistry
PubMed ID28409622
PubMed Central IDPMC5415871
Grant ListT32 AR007592 / AR / NIAMS NIH HHS / United States
R01 CA107331 / CA / NCI NIH HHS / United States
R01 GM058888 / GM / NIGMS NIH HHS / United States
R37 AR055099 / AR / NIAMS NIH HHS / United States
S10 RR017741 / RR / NCRR NIH HHS / United States