Regulation of type I adenylyl cyclase by calmodulin kinase IV in vivo

G A Wayman; J Wei; S Wong; D R Storm

doi:10.1128/MCB.16.11.6075

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Regulation of type I adenylyl cyclase by calmodulin kinase IV in vivo

Journal article

Open access

Peer reviewed

Regulation of type I adenylyl cyclase by calmodulin kinase IV in vivo

G A Wayman, J Wei, S Wong and D R Storm

Molecular and cellular biology, Vol.16(11), pp.6075-6082

11/1996

DOI: https://doi.org/10.1128/MCB.16.11.6075

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https://hdl.handle.net/2376/114612

PMCID: PMC231610

PMID: 8887637

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Abstract

Phosphorylation

Calcium-Calmodulin-Dependent Protein Kinase Type 4

Humans

Memory

Serine

Recombinant Proteins - biosynthesis

Kidney

Mice, Neurologic Mutants

Cell Membrane - metabolism

Binding Sites

Cyclic AMP - metabolism

Recombinant Proteins - metabolism

Adenylyl Cyclases - biosynthesis

Cell Line

Adenylyl Cyclases - deficiency

Alanine

Calcium - pharmacology

Mutagenesis, Site-Directed

Adenylyl Cyclases - metabolism

Point Mutation

Animals

Long-Term Potentiation

Mice

Kinetics

Calcium-Calmodulin-Dependent Protein Kinases - metabolism

Type I adenylyl cyclase is a neurospecific enzyme that is stimulated by Ca2+ and calmodulin (CaM). This enzyme couples the Ca2+ and cyclic AMP (cAMP) regulatory systems in neurons, and it may play an important role for some forms of synaptic plasticity. Mutant mice lacking type I adenylyl cyclase show deficiencies in spatial memory and altered long-term potentiation (Z. Wu, S. A. Thomas, Z. Xia, E. C. Villacres, R. D. Palmiter, and D. R. Storm, Proc. Natl. Acad. Sci. USA 92:220-224, 1995). Although type I adenylyl cyclase is synergistically stimulated by Ca2+ and G-protein-coupled receptors in vivo, very little is known about mechanisms for inhibition of the enzyme. Here, we report that type I adenylyl cyclase is inhibited by CaM kinase IV in vivo. Expression of constitutively active or wild-type CaM kinase IV inhibited Ca2+ stimulation of adenylyl cyclase activity without affecting basal or forskolin-stimulated activity. Type I adenylyl cyclase has two CaM kinase IV consensus phosphorylation sequences near its CaM binding domain at Ser-545 and Ser-552. Conversion of either serine to alanine by mutagenesis abolished CaM kinase IV inhibition of adenylyl cyclase. This suggests that the activity of this enzyme may be directly inhibited by CaM kinase IV phosphorylation. Type VIII adenylyl cyclase, another enzyme stimulated by CaM, was not inhibited by CaM kinase II or IV. We propose that CaM kinase IV may function as a negative feedback regulator of type I adenylyl cyclase and that CaM kinases may regulate cAMP levels in some cells.

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Details

Title: Regulation of type I adenylyl cyclase by calmodulin kinase IV in vivo
Creators: G A Wayman - Department of Pharmacology, University of Washington, Seattle, USA
J Wei
S Wong
D R Storm
Publication Details: Molecular and cellular biology, Vol.16(11), pp.6075-6082
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: HL 44948 / NHLBI NIH HHS
Identifiers: 99900548035201842
Language: English
Resource Type: Journal article