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Review
, 577 (2), 101-8

Protein Kinase A Catalytic Subunit Isoform PRKACA; History, Function and Physiology

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Review

Protein Kinase A Catalytic Subunit Isoform PRKACA; History, Function and Physiology

Rigney E Turnham et al. Gene.

Abstract

Our appreciation of the scope and influence of second messenger signaling has its origins in pioneering work on the cAMP-dependent protein kinase. Also called protein kinase A (PKA), this holoenzyme exists as a tetramer comprised of a regulatory (R) subunit dimer and two catalytic (C) subunits. Upon binding of two molecules of the second messenger cAMP to each R subunit, a conformational change in the PKA holoenzyme occurs to release the C subunits. These active kinases phosphorylate downstream targets to propagate cAMP responsive cell signaling events. This article focuses on the discovery, structure, cellular location and physiological effects of the catalytic subunit alpha of protein kinase A (encoded by the gene PRKACA). We also explore the potential role of this essential gene as a molecular mediator of certain disease states.

Keywords: A-kinase anchoring proteins; Catalytic subunits; Pathological cAMP signaling; Phosphorylation; Protein kinase A signaling; Regulatory subunits.

Figures

Figure 1
Figure 1. A) Alternate splicing of PRKACA exon 1: PKA Cα1 and PKA Cα2
This schematic depicts alternate splicing in exon 1 of PRKACA that gives rise to two distinct transcripts. B) Alternate forms of PKA Cα. This schematic shows the differences in the amino terminal amino acid sequence of Cα1 and Cα2. The remainder of the sequence is identical. C) The anchored PKA holoenzyme. This schematic representation of the protein components of an anchored PKA holoenzyme shows the C subunits (blue) and the R subunit dimer (green) in complex with an AKAP (yellow). Following stimulation of cAMP synthesis, the second messenger (black) binds to the regulatory subunits in a manner that releases the catalytic subunits to phosphorylate target substrates.
Figure 2
Figure 2. A lesion in chromosome 19 underlies the formation of a chimeric DNAJ-PKAc protein in patients with fibrolamellar hepatocellular carcinoma (FL-HCC)
A 400-kilobase pair deletion in chromosome 19 is found in almost all FL-HCC tumors sequenced. This deletion event results in the in-frame fusion of the first exon of DNAJB1 (orange) with exons two through ten of PRKACA (blue). This deletion event results in the production of a fusion pre-mRNA, and is eventually translated into a functional protein (DNAJ-PKAc).

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