Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo

J Wei; G Wayman; D R Storm

doi:10.1074/jbc.271.39.24231

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Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo

Journal article

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Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo

J Wei, G Wayman and D R Storm

The Journal of biological chemistry, Vol.271(39), pp.24231-24235

09/27/1996

DOI: https://doi.org/10.1074/jbc.271.39.24231

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https://hdl.handle.net/2376/112825

PMID: 8798667

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Abstract

Cell Line

Phosphorylation

Mutagenesis, Site-Directed

Humans

DNA, Complementary - genetics

Protein Kinase C - antagonists & inhibitors

Structure-Activity Relationship

Adenylyl Cyclases - metabolism

Recombinant Proteins

Phosphoserine - metabolism

Adenylyl Cyclase Inhibitors

Calcium - physiology

Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors

Calcium-Calmodulin-Dependent Protein Kinase Type 2

Calcium-Calmodulin-Dependent Protein Kinases - metabolism

Inhibition of type III adenylyl cyclase (III-AC) by intracellular Ca2+ in vivo provides a mechanism for attenuation of hormone-stimulated cAMP signals in olfactory epithelium, heart, and other tissues (Wayman, G. A., Impey, S., and Storm, D. R. (1995) J. Biol. Chem. 270, 21480-21486). Although the mechanism for Ca2+ inhibition of III-AC in vivo has not been defined, inhibition is not mediated by Gi, cAMP-dependent protein kinase, or protein kinase C. However, Ca2+ inhibition of III-AC is antagonized by KN-62, a CaM-dependent kinase inhibitor. In addition, constitutively activated CaM kinase II inhibits the enzyme. These data suggest that CaM kinase II regulates the activity of III-AC by direct phosphorylation or by an indirect mechanism involving phosphorylation of a protein that inhibits III-AC. Here we report that III-AC is phosphorylated in vivo when intracellular Ca2+ is increased and that phosphorylation is prevented by CaM-dependent kinase inhibitors. Site-directed mutagenesis of a CaM kinase II consensus site (Ser-1076 to Ala-1076) in III-AC greatly reduced Ca2+-stimulated phosphorylation and inhibition of III-AC in vivo. These data support the hypothesis that Ca2+ inhibition of III-AC is due to direct phosphorylation of the enzyme by CaM kinase II in vivo.

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Title: Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo
Creators: J Wei - Department of Pharmacology, University of Washington, Seattle, Washington 98195-7820, USA
G Wayman
D R Storm
Publication Details: The Journal of biological chemistry, Vol.271(39), pp.24231-24235
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: HL 44948 / NHLBI NIH HHS
Identifiers: 99900547781401842
Language: English
Resource Type: Journal article