Bold G protein α and βγ subunit regulation of mammalian adenylyl cyclases is modulated by protein kinase C

Gregor Ziminermann, Marcelo G. Kazanietz, Peter M. Blumberg, Ronald Taussig

Research output: Contribution to journalArticle

Abstract

The nine isoforms of mammalian adenylyl cyclase that have been identified by cDNA cloning are distinguished by their differential regulation by G protein and non- G protein inputs. We have investigated the effect of protein kinase C (PKC) on the regulatory properties of the two adenylyl cyclase isoforms (types II and IV) that are stimulated by G protein j subunits. Membranes from SF9 cells infected with recombinant baculoviruses encoding either AC II or AC IV were prepared and utilized as relatively homogeneous preparations of these adenylyl cyclase isoforms. Protein kinase C was purified from SF9 cells overexpressing the PKC Q isoform. Preincubating type II adenylyl cyclase with PKC a results in an enhancement of cyclase activity in response to forskolin. The PKC treatment also increases the sensitivity of AC II to stimulation by Gsa. In contrast, the activation of AC II by G protein 0-y is extensively blocked by this treatment. While types II and IV adenylyl cyclases exhibit identical regulatory patterns in response to G-protein regulators, they respond quite differently to PKC treatment. Unlike the type II isoform, the forskolin-stimulated activity of type IV adenylyl cyclase is not enhanced by PKC treatment. In addition PKC treatment of type IV blocks both the Gsα - and βγ- stimulated activities of this adenylyl cyclase isoform. These results suggest that phosphorylation of adenylyl cyclase isoforms by PKC can modulate the responsiveness of the cyclases to G protein subunits.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

Fingerprint

adenylate cyclase
Protein Subunits
protein kinase C
G-proteins
GTP-Binding Proteins
Adenylyl Cyclases
Protein Kinase C
Protein Isoforms
forskolin
Colforsin
protein subunits
Therapeutics
Phosphorylation
Baculoviridae
Cloning
Organism Cloning
phosphorylation
Complementary DNA
Chemical activation
Cell Membrane

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Bold G protein α and βγ subunit regulation of mammalian adenylyl cyclases is modulated by protein kinase C. / Ziminermann, Gregor; Kazanietz, Marcelo G.; Blumberg, Peter M.; Taussig, Ronald.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Ziminermann, Gregor ; Kazanietz, Marcelo G. ; Blumberg, Peter M. ; Taussig, Ronald. / Bold G protein α and βγ subunit regulation of mammalian adenylyl cyclases is modulated by protein kinase C. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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