title: Compartmentalization role of A-kinase anchoring proteins (AKAPs) in mediating protein kinase A (PKA) signaling and cardiomyocyte hypertrophy.
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.
authors.affiliation: Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan. amrababah@just.edu.jo.
authors.forename: Abeer
authors.initials: A
authors.lastname: Rababa'h
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Texas Medical Center, Houston, TX 77204, USA. svsuryavanshi@uh.edu.
authors.forename: Sonal
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Texas Medical Center, Houston, TX 77204, USA. svsuryavanshi@uh.edu.
authors.forename: Santosh V
authors.initials: SV
authors.lastname: Suryavanshi
authors.affiliation: Department of Cardiac Surgery, Queen Alia Heart Institute, Amman 11953, Jordan. Salah936@yahoo.com.
authors.forename: Salah Eldien
authors.initials: SE
authors.lastname: Altarabsheh
authors.affiliation: Department of Cardiovascular Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Salildeo@yahoo.co.in.
authors.forename: Salil V
authors.initials: SV
authors.lastname: Deo
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Texas Medical Center, Houston, TX 77204, USA. bkmcconn@central.uh.edu.
authors.forename: Bradley K
authors.initials: BK
authors.lastname: McConnell
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D054758:A Kinase Anchor Proteins; D017868:Cyclic AMP-Dependent Protein Kinases