Evolution of the cAMP-dependent protein kinase (PKA) catalytic subunit isoforms

PLoS One. 2017 Jul 25;12(7):e0181091. doi: 10.1371/journal.pone.0181091. eCollection 2017.


The 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase, or protein kinase A (PKA), pathway is one of the most versatile and best studied signaling pathways in eukaryotic cells. The two paralogous PKA catalytic subunits Cα and Cβ, encoded by the genes PRKACA and PRKACB, respectively, are among the best understood model kinases in signal transduction research. In this work, we explore and elucidate the evolution of the alternative 5' exons and the splicing pattern giving rise to the numerous PKA catalytic subunit isoforms. In addition to the universally conserved Cα1/Cβ1 isoforms, we find kinase variants with short N-termini in all main vertebrate classes, including the sperm-specific Cα2 isoform found to be conserved in all mammals. We also describe, for the first time, a PKA Cα isoform with a long N-terminus, paralogous to the PKA Cβ2 N-terminus. An analysis of isoform-specific variation highlights residues and motifs that are likely to be of functional importance.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Catalytic Domain*
  • Conserved Sequence
  • Cyclic AMP-Dependent Protein Kinases / chemistry*
  • Cyclic AMP-Dependent Protein Kinases / genetics*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Evolution, Molecular*
  • Exons
  • Humans
  • Introns
  • Models, Molecular
  • Phylogeny
  • Protein Conformation
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sequence Alignment


  • Protein Isoforms
  • Cyclic AMP-Dependent Protein Kinases

Grant support

This work was supported by University of Oslo (BSS)_2015/2017, http://www.uio.no/; Norwegian Cancer Society # 2284135, https://kreftforeningen.no/; Throne Holst (BSS) 2015/2016, http://www.uio.no/for-ansatte/arbeidsstotte/fa/finansiering/internt/med/imb/throne-holst/.