Complexity and diversity of mammalian adenylyl cyclases

Annu Rev Pharmacol Toxicol. 1996:36:461-80. doi: 10.1146/


Molecular cloning has permitted identification of several novel isoforms of mammalian adenylyl cyclase; these proteins now comprise a family of at least 10. All of the membrane-bound enzymes are activated by the alpha subunit of G alpha, a receptor-regulated, heterotrimeric guanine nucleotide-binding protein, and by the diterpene forskolin. Certain cyclases are also activated by Ca(2+)-calmodulin, while some are inhibited by the alpha subunits of the three Gi proteins. The discovery of new isoforms has also revealed unanticipated mechanisms of regulation, including activation or inhibition by the G-protein beta gamma subunit complex, inhibition by G(o) alpha, inhibition by Ca2+, and phosphorylation by protein kinases C and A. The effects of activators are often highly synergistic or conditional, suggesting function of these enyzmes as coincidence detectors. The plethora of receptors, G proteins, and adenylyl cyclases permits assembly of very complex signaling systems with a wide variety of integrative characteristics.

Publication types

  • Review

MeSH terms

  • Adenylyl Cyclases / chemistry
  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / isolation & purification
  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Cloning, Molecular
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Drug Synergism
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Tissue Distribution


  • Isoenzymes
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Calcium