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

ABSTRACT: Biochemical and structural studies demonstrate that S100A1 is involved in a Ca2+-dependent interaction with the type 2? and type 2? regulatory subunits of protein kinase A (PKA) (RII? and RII?) 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.

SUBMITTER: Melville Z

PROVIDER: S-EPMC5415871 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Melville Zephan Z Hernández-Ochoa Erick O EO Pratt Stephen J P SJP Liu Yewei Y Pierce Adam D AD Wilder Paul T PT Adipietro Kaylin A KA Breysse Daniel H DH Varney Kristen M KM Schneider Martin F MF Weber David J DJ

Biochemistry 20170418 17

Biochemical and structural studies demonstrate that S100A1 is involved in a Ca<sup>2+</sup>-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 ...[more]

PMID: 28409622

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