Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons

Duane D Hall; Monika A Davare; Mei Shi; Margaret L Allen; Michael Weisenhaus; G Stanley McKnight; Johannes W Hell

doi:10.1021/bi062217x

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Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons

Journal article

Peer reviewed

Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons

Duane D Hall, Monika A Davare, Mei Shi, Margaret L Allen, Michael Weisenhaus, G Stanley McKnight and Johannes W Hell

Biochemistry (Easton), Vol.46(6), pp.1635-1646

02/13/2007

DOI: 10.1021/bi062217x

PMID: 17279627

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Abstract

The cAMP-dependent protein kinase (PKA) regulates a wide array of cellular functions. In brain and heart PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation. Cav1.2 forms a complex with the beta2-adrenergic receptor, the trimeric GS protein, adenylyl cyclase, and PKA wherein highly localized signaling occurs [Davare, M. A., Avdonin, V., Hall, D. D., Peden, E. M., Burette, A., Weinberg, R. J., Horne, M. C., Hoshi, T., and Hell, J. W. (2001) Science 293, 98-101]. PKA primarily phosphorylates Cav1.2 on serine 1928 of the central, pore-forming alpha11.2 subunit. Here we demonstrate that the A-kinase anchor protein 150 (AKAP150) is critical for PKA-mediated regulation of Cav1.2 in the brain. AKAP150 and MAP2B specifically co-immunoprecipitate with Cav1.2 from rat brain. Recombinant AKAP75, the bovine homologue to rat AKAP150, binds directly to three different sites of alpha11.2. MAP2B from rat brain also interacts with these same sites in pull-down assays. Gene disruption of AKAP150 in mice dramatically reduces co-immunoprecipitation of PKA with Cav1.2 and prevents phosphorylation of serine 1928 upon beta-adrenergic stimulation in vivo. These results demonstrate the physiological relevance of PKA anchoring by AKAPs in general and AKAP150 specifically in the regulation of Cav1.2 in vivo.

Amino Acid Sequence

Serine - physiology

Receptors, Adrenergic, beta-2 - physiology

Microtubule-Associated Proteins - metabolism

Adaptor Proteins, Signal Transducing - isolation & purification

Rats

Calcium Channels, L-Type - physiology

Cytoskeletal Proteins - isolation & purification

Receptors, Adrenergic, beta-2 - drug effects

Mice, Knockout

Adaptor Proteins, Signal Transducing - physiology

Cyclic AMP-Dependent Protein Kinases - physiology

Animals

Signal Transduction - drug effects

Isoproterenol - pharmacology

A Kinase Anchor Proteins

Adaptor Proteins, Signal Transducing - genetics

Neurons - physiology

Calcium Channels, L-Type - isolation & purification

Signal Transduction - physiology

Mice

Phosphorylation - drug effects

Adaptor Proteins, Signal Transducing - metabolism

Details

Title: Subtitle: Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons
Creators: Duane D Hall - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242-1109, USA. duane-hall@uiowa.edu
Monika A Davare
Mei Shi
Margaret L Allen
Michael Weisenhaus
G Stanley McKnight
Johannes W Hell
Resource Type: Journal article
Publication Details: Biochemistry (Easton), Vol.46(6), pp.1635-1646
DOI: 10.1021/bi062217x
PMID: 17279627
ISSN: 0006-2960
eISSN: 1520-4995
Grant note: R01-GM32875 / NIGMS NIH HHS T32 DK07759 / NIDDK NIH HHS T32 HL07121 / NHLBI NIH HHS DA13410 / NIDA NIH HHS R01-NS035563 / NINDS NIH HHS R01-AG017502 / NIA NIH HHS
Language: English
Date published: 02/13/2007
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094875002771

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