Journal article
Targeting of Protein Phosphatases PP2A and PP2B to the C-terminus of the L-type Calcium Channel Cav1.2
Biochemistry (Easton), Vol.49(48), pp.10298-10307
12/07/2010
DOI: 10.1021/bi101018c
PMCID: PMC3075818
PMID: 21053940
Abstract
The L-type Ca
2+
channel Ca
v
1.2 forms macromolecular signaling complexes that comprise the β
2
adrenergic receptor, trimeric G
s
protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA
1
) for efficient signaling in heart and brain. The protein phosphatases PP2A and PP2B are part of this complex. PP2A counteracts increase in Ca
v
1.2 channel activity by PKA and other protein kinases, whereas PP2B can either augment or decrease Ca
v
1.2 currents in cardiomyocytes depending on the precise experimental conditions. We found that PP2A binds to two regions in the C-terminus of the central, pore-forming α
1
subunit of Ca
v
1.2: one region spans residues 1795-1818 and the other residues 1965-1971. PP2B binds immediately downstream of residue 1971. Injection of a peptide that contained residues 1965-1971 and displaced PP2A but not PP2B from endogenous Ca
v
1.2 increased basal and isoproterenol-stimulated L-type Ca
2+
currents in acutely isolated cardiomyocytes. Together with our biochemical data, these physiological results indicate that anchoring of PP2A at this site of Ca
v
1.2 in the heart negatively regulates cardiac L-type currents, likely by counterbalancing basal and stimulated phosphorylation that is mediated by PKA and possibly other kinases.
Details
- Title: Subtitle
- Targeting of Protein Phosphatases PP2A and PP2B to the C-terminus of the L-type Calcium Channel Cav1.2
- Creators
- Hui Xu - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAKenneth S Ginsburg - Department of Pharmacology, University of California, Davis, CA 95616-8636, USADuane D Hall - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAMaike Zimmermann - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAIvar S Stein - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAMingxu Zhang - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USASamvit Tandan - Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX 75390-8573Joseph A Hill - Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX 75390-8573Mary C Horne - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USADonald Bers - Department of Pharmacology, University of California, Davis, CA 95616-8636, USAJohannes W Hell - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA
- Resource Type
- Journal article
- Publication Details
- Biochemistry (Easton), Vol.49(48), pp.10298-10307
- DOI
- 10.1021/bi101018c
- PMID
- 21053940
- PMCID
- PMC3075818
- NLM abbreviation
- Biochemistry
- ISSN
- 0006-2960
- eISSN
- 1520-4995
- Language
- English
- Date published
- 12/07/2010
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094877102771
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