Regulation of the Adenylate Cyclase Signalling Pathway: Potential Role for the Phosphorylation of the Catalytic Unit by Protein Kinase A and Protein Kinase C

  • Takaaki Yoshimasa
  • Michel Bouvier
  • Jeffrey L. Benovic
  • Nourdine Amlaiky
  • Robert J. Lefkowitz
  • Marc G. Caron
Part of the Biochemical Endocrinology book series (BIOEND)


We have investigated the phosphorylation of the pure catalytic unit of adenylate cyclase by cyclic AMP-dependent protein kinase (PKA) and Ca2+/phospholipid-dependent protein kinase (PKC). The catalytic unit of adenylate cyclase from bovine striatum was purified to apparent homogeneity by sequential affinity chromatography on forskolin-Sepharose and wheat germ aggulutinin-agarose to a specific activity of 1.5 μ The enzyme migrates as a single band of M ~160,000 on sodium dodecyl sulfate-polyacrylamide electrophoresis gels and co-elutes with adenylate cyclase activity on steric-exclusion HPLC. The purified catalytic unit can be co-reconstituted with purified β2-adrenergic receptor and stimulatory guanine nucleotide regulatory protein (GS) resulting in their functional coupling. The enzyme can be phosphorylated by both PKA and PKC up to 0.9 mol of phosphate/mol of enzyme. Phosphorylation of the catalytic unit by PKA reduces the Gpp(NH)p-stimulated activity of the enzyme by 30% when co-reconstituted with GS, whereas PKC-phosphorylation of the enzyme enhances this activity by 25%. These results suggest that hormone-sensitive adenylate cyclase systems may be regulated in vivo by PKA- and PKC-dependent phosphorylation of their catalytic units.


Adenylate Cyclase Phorbol Ester Adenylate Cyclase Activity Phospholipid Vesicle Adenylate Cyclase System 
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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Takaaki Yoshimasa
    • 1
  • Michel Bouvier
    • 1
  • Jeffrey L. Benovic
    • 1
  • Nourdine Amlaiky
    • 1
  • Robert J. Lefkowitz
    • 1
  • Marc G. Caron
    • 1
  1. 1.Departments of Medicine, Biochemistry and Cell Biology Howard Hughes Medical InstituteDuke University Medical CenterDurhamUSA

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