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Int. J. Mol. Sci. 2015, 16(1), 218-229; doi:10.3390/ijms16010218

Compartmentalization Role of A-Kinase Anchoring Proteins (AKAPs) in Mediating Protein Kinase A (PKA) Signaling and Cardiomyocyte Hypertrophy

1
Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan
2
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Texas Medical Center, Houston, TX 77204, USA
3
Department of Cardiac Surgery, Queen Alia Heart Institute, Amman 11953, Jordan
4
Department of Cardiovascular Surgery, Case Western Reserve University, Cleveland, OH 44106, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Jens Schlossmann
Received: 24 September 2014 / Accepted: 18 December 2014 / Published: 24 December 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
View Full-Text   |   Download PDF [675 KB, uploaded 24 December 2014]

Abstract

The Beta-adrenergic receptors (β-ARs) stimulation enhances contractility through protein kinase-A (PKA) substrate phosphorylation. This PKA signaling is conferred in part by PKA binding to A-kinase anchoring proteins (AKAPs). AKAPs coordinate multi-protein signaling networks that are targeted to specific intracellular locations, resulting in the localization of enzyme activity and transmitting intracellular actions of neurotransmitters and hormones to its target substrates. In particular, mAKAP (muscle-selective AKAP) has been shown to be present on the nuclear envelope of cardiomyocytes with various proteins including: PKA-regulatory subunit (RIIα), phosphodiesterase-4D3, protein phosphatase-2A, and ryanodine receptor (RyR2). Therefore, through the coordination of spatial-temporal signaling of proteins and enzymes, mAKAP controls cyclic-adenosine monophosphate (cAMP) levels very tightly and functions as a regulator of PKA-mediated substrate phosphorylation leading to changes in calcium availability and myofilament calcium sensitivity. The goal of this review is to elucidate the critical compartmentalization role of mAKAP in mediating PKA signaling and regulating cardiomyocyte hypertrophy by acting as a scaffolding protein. Based on our literature search and studying the structure–function relationship between AKAP scaffolding protein and its binding partners, we propose possible explanations for the mechanism by which mAKAP promotes cardiac hypertrophy. View Full-Text
Keywords: hypertrophy; protein kinase A (PKA); A kinase anchoring protein (AKAP); contractility hypertrophy; protein kinase A (PKA); A kinase anchoring protein (AKAP); contractility
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Rababa'h, A.; Singh, S.; Suryavanshi, S.V.; Altarabsheh, S.E.; Deo, S.V.; McConnell, B.K. Compartmentalization Role of A-Kinase Anchoring Proteins (AKAPs) in Mediating Protein Kinase A (PKA) Signaling and Cardiomyocyte Hypertrophy. Int. J. Mol. Sci. 2015, 16, 218-229.

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