Identification, cloning and characterization of a novel 47 kDa murine PKA C subunit homologous to human and bovine Cβ2

Funderud, Ane; Henanger, Heidi; Hafte, Tilahun Tolesa; Amieux, Paul S.; Ørstavik, Sigurd; Skålhegg, Bjørn Steen

doi:10.1186/1471-2091-7-20

Cited by 20 publications

(8 citation statements)

References 29 publications

(44 reference statements)

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“…A number of isoforms of human PRKACB have been identified with alternative splicing of exons 5′ of exon 2 (Fig. 1A), encoding at least the following proteins: Cβ1, Cβ2, Cβ3, Cβ4, Cβ3ab, Cβ3b, Cβ3abc, Cβ4ab, Cβ4b, and Cβ4abc [28]–[33]. In addition, Cβ variants formed by skipping of exon 4 are expressed in the brain of higher primates.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary Paths of the cAMP-Dependent Protein Kinase (PKA) Catalytic Subunits

et al. 2013

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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.

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Section: Introductionmentioning

confidence: 99%

Evolutionary Paths of the cAMP-Dependent Protein Kinase (PKA) Catalytic Subunits

et al. 2013

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“…Cα1 and Cα2 have non-identical N-terminal ends encoded by alternative use of two exons (1a and 1b, mouse terminology) located upstream of exon 2 in the murine Cα gene. The Cβ gene encodes a number of products identified in various species and have been designated Cβ1, Cβ2, Cβ3, Cβ4, Cβ3ab, Cβ3b, Cβ3abc, Cβ4ab, Cβ4b, Cβ4abc [ 12 - 17 ]. As is the case for the Cα forms, all the Cβ variants have variable N-terminal ends which are encoded by different exons upstream of exon 2 in the Cβ gene [14;15].…”

Section: Introductionmentioning

confidence: 99%

The testis-specific Cα2 subunit of PKA is kinetically indistinguishable from the common Cα1 subunit of PKA

et al. 2011

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BackgroundThe two variants of the α-form of the catalytic (C) subunit of protein kinase A (PKA), designated Cα1 and Cα2, are encoded by the PRKACA gene. Whereas Cα1 is ubiquitous, Cα2 expression is restricted to the sperm cell. Cα1 and Cα2 are encoded with different N-terminal domains. In Cα1 but not Cα2 the N-terminal end introduces three sites for posttranslational modifications which include myristylation at Gly1, Asp-specific deamidation at Asn2 and autophosphorylation at Ser10. Previous reports have implicated specific biological features correlating with these modifications on Cα1. Since Cα2 is not modified in the same way as Cα1 we tested if they have distinct biochemical activities that may be reflected in different biological properties.ResultsWe show that Cα2 interacts with the two major forms of the regulatory subunit (R) of PKA, RI and RII, to form cAMP-sensitive PKAI and PKAII holoenzymes both in vitro and in vivo as is also the case with Cα1. Moreover, using Surface Plasmon Resonance (SPR), we show that the interaction patterns of the physiological inhibitors RI, RII and PKI were comparable for Cα2 and Cα1. This is also the case for their potency to inhibit catalytic activities of Cα2 and Cα1.ConclusionWe conclude that the regulatory complexes formed with either Cα1 or Cα2, respectively, are indistinguishable.

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“…Cα1 and Cβ1 are more than 90% identical at the amino acid level and are ubiquitously expressed. CαS has only been identified in sperm cells [ 28 ], Cβ2 is predominantly expressed in lymphoid cells [ 29 , 30 ], and Cβ3 and Cβ4 and their abc variants are mainly expressed in neuronal tissues [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Protein kinase A type I activates a CRE-element more efficiently than protein kinase A type II regardless of C subunit isoform

et al. 2011

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BackgroundProtein kinase A type I (PKAI) and PKAII are expressed in most of the eukaryotic cells examined. PKA is a major receptor for cAMP and specificity is achieved partly through tissue-dependent expression and subcellular localization of subunits with different biochemical properties. In addition posttranslational modifications help fine tune PKA activity, distribution and interaction in the cell. In spite of this the functional significance of two forms of PKA in one cell has not been fully determined. Here we have tested the ability of PKAI and PKAII formed by expression of the regulatory (R) subunits RIα or RIIα in conjunction with Cα1 or Cβ2 to activate a co-transfected luciferace reporter gene, controlled by the cyclic AMP responsive element-binding protein (CREB) in vivo.ResultsWe show that PKAI when expressed at equal levels as PKAII was significantly (p < 0.01) more efficient in inducing Cre-luciferace activity at saturating concentrations of cAMP. This result was obtained regardless of catalytic subunit identity.ConclusionWe suggest that differential effects of PKAI and PKAII in inducing Cre-luciferace activity depend on R and not C subunit identity.

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Identification, cloning and characterization of a novel 47 kDa murine PKA C subunit homologous to human and bovine Cβ2

Cited by 20 publications

References 29 publications

Evolutionary Paths of the cAMP-Dependent Protein Kinase (PKA) Catalytic Subunits

Evolutionary Paths of the cAMP-Dependent Protein Kinase (PKA) Catalytic Subunits

The testis-specific Cα2 subunit of PKA is kinetically indistinguishable from the common Cα1 subunit of PKA

Protein kinase A type I activates a CRE-element more efficiently than protein kinase A type II regardless of C subunit isoform

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