Adenylyl cyclase 6 is selectively regulated by protein kinase A phosphorylation in a region involved in Galphas stimulation

Y Chen, A Harry, J Li, M J Smit, X Bai, R Magnusson, J P Pieroni, G Weng, R Iyengar

Research output: Contribution to JournalArticleAcademicpeer-review


Receptors activate adenylyl cyclases through the Galphas subunit. Previous studies from our laboratory have shown in certain cell types that express adenylyl cyclase 6 (AC6), heterologous desensitization included reduction of the capability of adenylyl cyclases to be stimulated by Galphas. Here we further analyze protein kinase A (PKA) effects on adenylyl cyclases. PKA treatment of recombinant AC6 in insect cell membranes results in a selective loss of stimulation by high (>10 nM) concentrations of Galphas. Similar treatment of AC1 or AC2 did not affect Galphas stimulation. Conversion of Ser-674 in AC6 to an Ala blocks PKA phosphorylation and PKA-mediated loss of Galphas stimulation. A peptide encoding the region 660-682 of AC6 blocks stimulation of AC6 and AC2 by high concentrations of Galphas. Substitution of Ser-674 to Asp in the peptide renders the peptide ineffective, indicating that the region 660-682 of AC6 is involved in regulation of signal transfer from Galphas. This region contains a conserved motif present in most adenylyl cyclases; however, the PKA phosphorylation site is unique to members of the AC6 family. These observations suggest a mechanism of how isoform selective regulatory diversity can be obtained within conserved regions involved in signal communication.

Original languageEnglish
Pages (from-to)14100-4
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
Publication statusPublished - 9 Dec 1997


  • Adenylyl Cyclases
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Cell Membrane
  • Cyclic AMP-Dependent Protein Kinases
  • GTP-Binding Proteins
  • Humans
  • Insecta
  • Isoenzymes
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.


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