G Protein–Coupled Receptor Kinases in Cardiovascular Disease: Why “Where” Matters

Kamal, Fadia; Travers, Joshua G; Blaxall, Burns C.

doi:10.1016/j.tcm.2012.07.023

Cited by 21 publications

(25 citation statements)

References 68 publications

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“…A characteristic feature of GPCRs is their deactivation by internalization and phosphorylation following sustained stimulation by high concentrations of their ligands (Kamal et al, 2012). Such deactivation of IP and E4 has been reported previously (Desai et al, 2000;Nilius et al, 2000).…”

Section: Effects Of Prostanoid Receptor Activation Followed By Desenssupporting

confidence: 65%

Prostanoids regulate angiogenesis acting primarily on IP and EP4 receptors

Hoang

Allison

Murray

et al. 2015

Microvascular Research

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Section: Effects Of Prostanoid Receptor Activation Followed By Desenssupporting

confidence: 65%

Prostanoids regulate angiogenesis acting primarily on IP and EP4 receptors

Hoang

Allison

Murray

et al. 2015

Microvascular Research

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“…Multiple GRK isoforms have been shown to play distinct roles in mediating receptor signaling responses in different tissues 33 , but generalized ablation of GRKs would impact βAR signaling regardless of the role of V1AR in regulating βAR desensitization. Thus, to specifically explore the impact of GRK-dependent V1AR signaling, we developed a V1AR construct lacking all possible C-terminal GRK phosphorylation sites (GRK − V1AR, Fig.…”

Section: Resultsmentioning

confidence: 99%

β-Adrenergic Receptor–Mediated Cardiac Contractility Is Inhibited via Vasopressin Type 1A-Receptor–Dependent Signaling

Tilley¹,

Zhu²,

Myers³

et al. 2014

Circulation

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Background Enhanced arginine vasopressin (AVP) levels are associated with increased mortality during end-stage human heart failure (HF), and cardiac AVP type 1A receptor (V1AR) expression becomes increased. Additionally, mice with cardiac-restricted V1AR overexpression develop cardiomyopathy and decreased β-adrenergic receptor (βAR) responsiveness. This led us to hypothesize that V1AR signaling regulated βAR responsiveness and in doing so contributes to HF development. Methods and Results Transaortic constriction resulted in decreased cardiac function and βAR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased βAR ligand affinity, as well as βAR-induced Ca2+ mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of βAR responsiveness was demonstrated to occur in a previously unrecognized Gq protein-independent/GRK-dependent manner. Conclusions This newly discovered relationship between cardiac V1AR and βAR may be informative for the treatment of patients with acute decompensated HF and elevated AVP.

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“…The canonical view is that internalization of GPCRs is part of the receptor desensitization process and involves receptor phosphorylation by G protein-coupled receptor kinases, recruitment of beta-arrestin and consequent GPCR internalization (Kamal et al, 2012). Once internalized, GPCRs can be re-exposed, in their inactive state, at the plasma membrane or, alternatively, can be targeted for degradation (Zhang and Eggert, 2013).…”

Section: Compartmentalization Of the Camp/pka Signaling Pathway Comentioning

confidence: 99%

cAMP signaling in subcellular compartments

Lefkimmiatis

Zaccolo

2014

Pharmacology & Therapeutics

168

149

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In the complex microcosm of a cell, information security and its faithful transmission are critical for maintaining internal stability. To achieve a coordinated response of all its parts to any stimulus the cell must protect the information received from potentially confounding signals. Physical segregation of the information transmission chain ensures that only the entities able to perform the encoded task have access to the relevant information. The cAMP intracellular signaling pathway is an important system for signal transmission responsible for the ancestral ‘flight or fight’ response and involved in the control of critical functions including frequency and strength of heart contraction, energy metabolism and gene transcription. It is becoming increasingly apparent that the cAMP signaling pathway uses compartmentalization as a strategy for coordinating the large number of key cellular functions under its control. Spatial confinement allows the formation of cAMP signaling “hot spots” at discrete subcellular domains in response to specific stimuli, bringing the information in proximity to the relevant effectors and their recipients, thus achieving specificity of action. In this report we discuss how the different constituents of the cAMP pathway are targeted and participate in the formation of cAMP compartmentalized signaling events. We illustrate a few examples of localized cAMP signaling, with a particular focus on the nucleus, the sarcoplasmic reticulum and the mitochondria. Finally, we discuss the therapeutic potential of interventions designed to perturb specific cAMP cascades locally.

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G Protein–Coupled Receptor Kinases in Cardiovascular Disease: Why “Where” Matters

Cited by 21 publications

References 68 publications

Prostanoids regulate angiogenesis acting primarily on IP and EP4 receptors

Prostanoids regulate angiogenesis acting primarily on IP and EP4 receptors

β-Adrenergic Receptor–Mediated Cardiac Contractility Is Inhibited via Vasopressin Type 1A-Receptor–Dependent Signaling

cAMP signaling in subcellular compartments

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