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

BMC Biochem. 2011 Aug 3:12:40. doi: 10.1186/1471-2091-12-40.

Abstract

Background: The 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.

Results: We 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.

Conclusion: We conclude that the regulatory complexes formed with either Cα1 or Cα2, respectively, are indistinguishable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / metabolism*
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / metabolism
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Activation
  • Holoenzymes
  • Humans
  • Isoenzymes
  • Male
  • Organ Specificity
  • Spermatozoa / enzymology
  • Surface Plasmon Resonance
  • Testis / enzymology*

Substances

  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Holoenzymes
  • Isoenzymes
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • Cyclic AMP-Dependent Protein Kinases
  • PRKACA protein, human