G-protein-coupled receptor kinases in cardiovascular conditions: focus on G-protein-coupled receptor kinase 2, a gain in translational medicine

2009 ◽  
Vol 3 (5) ◽  
pp. 525-540 ◽  
Author(s):  
Alfonso Campanile ◽  
Guido Iaccarino
Keyword(s):  
G Protein ◽  
Translational Medicine ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Receptor Kinases ◽  
G Protein Coupled

scholarly journals Expression of G-protein-coupled receptor kinases in pregnant term and non-pregnant human myometrium

1999 ◽  
Vol 162 (3) ◽  
pp. 401-408 ◽  
Author(s):  
CB Brenninkmeijer ◽  
SA Price ◽  
A Lopez Bernal ◽  
S Phaneuf
Keyword(s):  
G Protein ◽  
Human Myometrium ◽  
Receptor Kinase ◽  
Uterine Contractility ◽  
G Protein Coupled Receptor ◽  
Myometrial Cells ◽  
Reverse Transcription Pcr ◽  
Receptor Kinases ◽  
G Protein Coupled ◽  
Receptor Desensitisation

There is evidence for hormonal receptor desensitisation in human myometrium, but little is known about the mechanisms involved in the loss of myometrial response to agonists such as beta(2)-adrenergic agonists, prostaglandin gamma and oxytocin. It is well known that the receptors for these hormones are coupled to G-proteins. The first step of receptor desensitisation is the phosphorylation of activated receptors by a G-protein-coupled receptor kinase (GRK). GRKs are members of a multigene family and the various subtypes differ in their localisation, regulation and mode of action. We have used Western blotting and reverse transcription PCR to identify the GRKs present in human myometrium from pregnant and non-pregnant women as well as in cultured human myometrial cells. We have found that human myometrium expresses the GRK subtypes 2, 4gamma, 5 and 6. On the other hand, GRK3 and the isoforms GRK4alpha, beta and delta were not found in myometrial tissue. Our data indicate that GRK2 is only expressed in pregnant term myometrium and is not found in non-pregnant tissue. Moreover, GRK6 appears to be expressed at a much higher level in pregnant term tissue than in non-pregnant myometrium. Our observations suggest that GRK2 and GRK6 may contribute to the regulation of uterine contractility at term. Further work is necessary to determine whether GRKs and receptor desensitisation play a role in disorders of uterine contractility.

The Drosophila G-protein-coupled receptor kinase homologue Gprk2 is required for egg morphogenesis

Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2591-2602 ◽  
Author(s):  
L.E. Schneider ◽  
A.C. Spradling
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Follicle Cells ◽  
Protein Signaling ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Receptor Kinases ◽  
A Cell ◽  
External Signals ◽  
G Protein Coupled

G protein signaling is a widely utilized form of extracellular communication that is mediated by a family of serpentine receptors containing seven transmembrane domains. In sensory neurons, cardiac muscle and other tissues, G protein-coupled receptors are desensitized through phosphorylation by a family of kinases, the G protein-coupled receptor kinases (GRKs). Desensitization allows a cell to decrease its response to a given signal, in the continued presence of that signal. We have identified a Drosophila mutant, gprk2(6936) that disrupts expression of a putative member of the GRK family, the G protein-coupled receptor kinase 2 gene (Gprk2). This mutation affects Gprk2 gene expression in the ovaries and renders mutant females sterile. The mutant eggs contain defects in several anterior eggshell structures that are produced by specific subsets of migratory follicle cells. In addition, rare eggs that become fertilized display gross defects in embryogenesis. These observations suggest that developmental signals transduced by G protein-coupled receptors are regulated by receptor phosphorylation. Based on the known functions of G protein-coupled receptor kinases, we speculate that receptor desensitization assists cells that are migrating or undergoing shape changes to respond rapidly to changing external signals.

scholarly journals The G Protein-Coupled Receptor Kinases (GRKs) in Chemokine Receptor-Mediated Immune Cell Migration: From Molecular Cues to Physiopathology

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 75
Author(s):  
Marta Laganà ◽  
Géraldine Schlecht-Louf ◽  
Françoise Bachelerie
Keyword(s):  
G Protein ◽  
Chemokine Receptor ◽  
Immune Cell ◽  
Neutrophil Migration ◽  
G Protein Coupled Receptor ◽  
Receptor Kinases ◽  
Immune Cell Migration ◽  
And Migration ◽  
G Protein Coupled ◽  
Gpcr Desensitization

Although G protein-coupled receptor kinases (GRKs) have long been known to regulate G protein-coupled receptor (GPCR) desensitization, their more recently characterized functions as scaffolds and signalling adapters underscore that this small family of proteins governs a larger array of physiological functions than originally suspected. This review explores how GRKs contribute to the complex signalling networks involved in the migration of immune cells along chemokine gradients sensed by cell surface GPCRs. We outline emerging evidence indicating that the coordinated docking of several GRKs on an active chemokine receptor determines a specific receptor phosphorylation barcode that will translate into distinct signalling and migration outcomes. The guidance cues for neutrophil migration are emphasized based on several alterations affecting GRKs or GPCRs reported to be involved in pathological conditions.

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