| GRK6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | GRK6 , GPRK6, G protein-coupled receptor kinase 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 600869 MGI: 1347078 HomoloGene: 37570 GeneCards: GRK6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most highly similar to GRK4 and GRK5. [5] [6] [7] The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.
G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents receptor stimulation of heterotrimeric G protein transducer proteins, blocking their cellular signaling and resulting in receptor desensitization. Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell surface and also preventing additional activation. Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the GRK/arrestin system serves as a complex signaling switch for G protein-coupled receptors. [8]
GRK6 and the closely related GRK5 phosphorylate receptors at sites that encourage arrestin-mediated signaling rather than arrestin-mediated receptor desensitization, internalization and trafficking (in contrast to GRK2 and GRK3, which have the opposite effect). [9] [10] This difference is one basis for pharmacological biased agonism (also called functional selectivity), where a drug binding to a receptor may bias that receptor's signaling toward a particular subset of the actions stimulated by that receptor. [11] [12]
GRK6 is widely and relatively evenly expressed throughout the body, but with particularly high expression in immune cells. [6] GRK6 exists in three splice variants that differ in the carboxyl terminal region that regulates membrane association: one form is palmitoylated, another contains a lipid-binding polybasic domain, and the third is truncated and has neither. [13] In the mouse, GRK6 regulates the D2 dopamine receptor in the striatum region of the brain, and loss of GRK6 leads to increased sensitivity to psychostimulant drugs that act through dopamine. [14] Overexpression of GRK6 in the striatum in a rat model of Parkinson's disease improves drug-induced movement disorder (tardive dyskinesia) symptoms arising from L-DOPA therapy. [15] In mouse immune cells, GRK6 is important for chemotaxis of B-lymphocytes and T-lymphocytes in response to the chemoattractant CXCL12, [16] and of neutrophils to sites of injury in response to leukotriene B4. [17]
ADP-ribosylation factor 6 (ARF6) is a member of the ADP ribosylation factor family of GTP-binding proteins. ARF6 has a variety of cellular functions that are frequently involved in trafficking of biological membranes and transmembrane protein cargo. ARF6 has specifically been implicated in endocytosis of plasma membrane proteins and also, to a lesser extent, plasma membrane protein recycling.
Arrestins are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors (GPCRs) in the visual rhodopsin system by Hermann Kühn, Scott Hall, and Ursula Wilden and in the β-adrenergic system by Martin J. Lohse and co-workers.
G protein-coupled receptor kinases are a family of protein kinases within the AGC group of kinases. Like all AGC kinases, GRKs use ATP to add phosphate to Serine and Threonine residues in specific locations of target proteins. In particular, GRKs phosphorylate intracellular domains of G protein-coupled receptors (GPCRs). GRKs function in tandem with arrestin proteins to regulate the sensitivity of GPCRs for stimulating downstream heterotrimeric G protein and G protein-independent signaling pathways.
G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ADRBK1 gene. GRK2 was initially called Beta-adrenergic receptor kinase, and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK3(βARK2).
Rhodopsin kinase is a serine/threonine-specific protein kinase involved in phototransduction. This enzyme catalyses the following chemical reaction:
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 protein domains. It is commonly referred to as PKB, or by both names as "Akt/PKB".
Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.
Sodium-hydrogen antiporter 3 regulator 1 is a regulator of Sodium-hydrogen antiporter 3. It is encoded by the gene SLC9A3R1. It is also known as ERM Binding Protein 50 (EBP50) or Na+/H+ Exchanger Regulatory Factor (NHERF1). It is believed to interact via long-range allostery, involving significant protein dynamics.
The alpha-1B adrenergic receptor (α1B-adrenoreceptor), also known as ADRA1B, is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it. The crystal structure of the α1B-adrenergic receptor has been determined in complex with the inverse agonist (+)-cyclazosin.
Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene.
In enzymology, a beta-adrenergic-receptor kinase is an enzyme that catalyzes the chemical reaction:
Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 gene.
Serine/threonine-protein kinase D1 is an enzyme that in humans is encoded by the PRKD1 gene.
ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene.
Cytohesin-2 is a protein that in humans is encoded by the CYTH2 gene.
G protein-coupled receptor kinase 5 is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases, and is most highly similar to GRK4 and GRK6. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.
G protein-coupled receptor kinase 4 (GRK4) is an enzyme that is encoded by the GRK4 gene in humans.
Arrestin-C, also known as retinal cone arrestin-3, is a protein that in humans is encoded by the ARR3 gene.
Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the DVL2 gene.
G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ADRBK2 gene. GRK3 was initially called Beta-adrenergic receptor kinase 2 (βARK-2), and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK2.
PDB gallery | |
|---|---|
|
 | This article on a gene on human chromosome 5 is a stub. You can help Wikipedia by expanding it. |
