title: Evolutionary paths of the cAMP-dependent protein kinase (PKA) catalytic subunits.
abstract: 3',5'-cyclic adenosine monophosphate (cAMP) dependent protein kinase or protein kinase A (PKA) has served as a prototype for the large family of protein kinases that are crucially important for signal transduction in eukaryotic cells. The PKA catalytic subunits Cα and Cβ, encoded by the two genes PRKACA and PRKACB, respectively, are among the best understood and characterized human kinases. Here we have studied the evolution of this gene family in chordates, arthropods, mollusks and other animals employing probabilistic methods and show that Cα and Cβ arose by duplication of an ancestral PKA catalytic subunit in a common ancestor of vertebrates. The two genes have subsequently been duplicated in teleost fishes. The evolution of the PRKACG retroposon in simians was also investigated. Although the degree of sequence conservation in the PKA Cα/Cβ kinase family is exceptionally high, a small set of signature residues defining Cα and Cβ subfamilies were identified. These conserved residues might be important for functions that are unique to the Cα or Cβ clades. This study also provides a good example of a seemingly simple phylogenetic problem which, due to a very high degree of sequence conservation and corresponding weak phylogenetic signals, combined with problematic nonphylogenetic signals, is nontrivial for state-of-the-art probabilistic phylogenetic methods.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Søberg
authors.forename: Tore
authors.initials: T
authors.lastname: Jahnsen
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Rognes
authors.forename: Bjørn S
authors.initials: BS
authors.lastname: Skålhegg
authors.forename: Jon K
authors.initials: JK
authors.lastname: Laerdahl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D043344:Chordata / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D018626:Retroelements / Q000235:genetics; D012641:Selection, Genetic
chemical_list: D018626:Retroelements; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human; C517760:PRKACB protein, human