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In [[biochemistry]] and [[signal transduction]], '''G-protein-coupled receptor kinases''' are a "family of serine-threonine kinases that are specific for [[G-protein-coupled receptor]]s. They are regulatory proteins that play a role in G-protein-coupled receptor | {{subpages}} | ||
In [[biochemistry]] and [[signal transduction]], '''G-protein-coupled receptor kinases''' are a "family of serine-threonine kinases that are specific for [[G-protein-coupled receptor]]s. They are regulatory proteins that play a role in [[G-protein-coupled receptor]] desensitization."<ref>{{MeSH}}</ref> "G protein-coupled receptor kinases (GRKs) play an important role in phosphorylating and regulating the activity of a variety of G protein-coupled receptors."<ref>{{OMIM|600870}}</ref> | |||
In [[signal transduction]], [[cell surface receptor]]s may activate [[second messenger system]]s such as adenyl cyclase-[[cyclic AMP]] and [[cyclic GMP]] which then may activate [[protein kinase]]s such as [[G-protein-coupled receptor kinase]] which then affect downstream targets (see [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=receptor,kinase,G-protein-coupled&rid=mcb.figgrp.5742 figure]).<ref name="isbn0-7167-3136-3">{{cite book |author=Lodish, Harvey F. |authorlink= |editor= |others= |title=Molecular cell biology |edition= |language= |publisher=Scientific American Books |location=New York |year=1999 |origyear= |chapter=20.1. Overview of Extracellular Signaling|chapterurl=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.section.5717|pages= |quote= |isbn=0-7167-3136-3 |oclc= |doi= |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb |accessdate=}}</ref> | |||
==Classification== | |||
* [[G-protein-coupled receptor kinase 1]] (GRK1) is "a protein-serine-threonine kinase that is found in photoreceptor cells. It mediates light-dependent phosphorylation of rhodopsin and plays an important role in phototransduction."<ref>{{MeSH|G-protein-coupled receptor kinase 1}}</ref> | |||
* beta-[[adrenergic receptor]] kinases | |||
** [[G-protein-coupled receptor kinase 2]] (GRK2) , also called beta-adrenergic receptor kinase 1 (ADRBK1), is "a ubiquitously expressed g-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of beta-[[adrenergic receptor]]s. It may play an essential role in regulating myocardial contractile response."<ref>{{MeSH|G-protein-coupled receptor kinase 2}}</ref> | |||
** [[G-protein-coupled receptor kinase 3]] (GRK3) , also called beta-adrenergic receptor kinase 2 (ADRBK2), is "a ubiquitously expressed g-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of beta-[[adrenergic receptor]]s and a variety of other g-protein-coupled-receptors. Although it is highly homologous to g-protein-coupled receptor kinase 2, it is not considered to play an essential role in regulating myocardial contractile response."<ref>{{MeSH|G-protein-coupled receptor kinase 3}}</ref> | |||
* [[G-protein-coupled receptor kinase 4]] (GRK4) is "a G-protein-coupled receptor kinase subtype that is primarily expressed in the [[testes]] and [[brain]]. Variants of this subtype exist due to multiple alternative splicing of its mRNA."<ref>{{MeSH|G-protein-coupled receptor kinase 4}}</ref> | |||
* [[G-protein-coupled receptor kinase 5]] (GRK5) is "a g-protein-coupled receptor kinase subtype that is primarily expressed in the myocardium and may play a role in the regulation of cardiac function."<ref>{{MeSH|G-protein-coupled receptor kinase 5}}</ref> | |||
==Pharmacogenomics== | ==Pharmacogenomics== | ||
Regarding the treatment of [[heart failure]], there is conflicting evidence whether [[beta- | ===Heart failure=== | ||
Regarding the treatment of [[heart failure]], there is conflicting evidence whether [[adrenergic beta-antagonist]]s are as effective in African-American patients as in Anglo patients.<ref name="pmid12742294">{{cite journal |author=Shekelle PG, Rich MW, Morton SC, ''et al'' |title=Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials |journal=J. Am. Coll. Cardiol. |volume=41 |issue=9 |pages=1529–38 |year=2003 |pmid=12742294 |doi=}}</ref> This may be due to a polymorphism in African-American patients of the G protein–coupled [[cell surface receptor]] kinase 5 (GRK5) that confers a natural "genetic beta-blockade".<ref name="pmid18425130">{{cite journal |author=Liggett SB, Cresci S, Kelly RJ, ''et al.'' |title=A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure |journal=Nat. Med. |volume=14 |issue=5 |pages=510–7 |year=2008 |month=May |pmid=18425130 |pmc=2596476 |doi=10.1038/nm1750 |url=http://dx.doi.org/10.1038/nm1750 |issn=}}</ref><ref>{{OMIM|600870}}</ref> | |||
G protein–coupled [[cell surface receptor]] kinase 2 (GRK2) [[genetic polymorphism]]s may also affect the response to [[adrenergic beta-antagonist]]s.<ref>{{OMIM|109635}}</ref> | |||
===Asthma=== | |||
[[Genetic polymorphism]]s may affect the response to [[adrenergic beta-antagonist]]s by patients of African descent.<ref name="pmid18622265">{{cite journal |author=Wang WC, Mihlbachler KA, Bleecker ER, Weiss ST, Liggett SB |title=A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted desensitization of beta2-adrenergic receptors |journal=Pharmacogenet. Genomics |volume=18 |issue=8 |pages=729–32 |year=2008 |month=August |pmid=18622265 |doi=10.1097/FPC.0b013e32830967e9 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1744-6872&volume=18&issue=8&spage=729 |issn=}}</ref> | |||
==References== | ==References== | ||
<references/> | <references/>[[Category:Suggestion Bot Tag]] | ||
Latest revision as of 16:00, 19 August 2024
In biochemistry and signal transduction, G-protein-coupled receptor kinases are a "family of serine-threonine kinases that are specific for G-protein-coupled receptors. They are regulatory proteins that play a role in G-protein-coupled receptor desensitization."[1] "G protein-coupled receptor kinases (GRKs) play an important role in phosphorylating and regulating the activity of a variety of G protein-coupled receptors."[2]
In signal transduction, cell surface receptors may activate second messenger systems such as adenyl cyclase-cyclic AMP and cyclic GMP which then may activate protein kinases such as G-protein-coupled receptor kinase which then affect downstream targets (see figure).[3]
Classification
- G-protein-coupled receptor kinase 1 (GRK1) is "a protein-serine-threonine kinase that is found in photoreceptor cells. It mediates light-dependent phosphorylation of rhodopsin and plays an important role in phototransduction."[4]
- beta-adrenergic receptor kinases
- G-protein-coupled receptor kinase 2 (GRK2) , also called beta-adrenergic receptor kinase 1 (ADRBK1), is "a ubiquitously expressed g-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of beta-adrenergic receptors. It may play an essential role in regulating myocardial contractile response."[5]
- G-protein-coupled receptor kinase 3 (GRK3) , also called beta-adrenergic receptor kinase 2 (ADRBK2), is "a ubiquitously expressed g-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of beta-adrenergic receptors and a variety of other g-protein-coupled-receptors. Although it is highly homologous to g-protein-coupled receptor kinase 2, it is not considered to play an essential role in regulating myocardial contractile response."[6]
- G-protein-coupled receptor kinase 4 (GRK4) is "a G-protein-coupled receptor kinase subtype that is primarily expressed in the testes and brain. Variants of this subtype exist due to multiple alternative splicing of its mRNA."[7]
- G-protein-coupled receptor kinase 5 (GRK5) is "a g-protein-coupled receptor kinase subtype that is primarily expressed in the myocardium and may play a role in the regulation of cardiac function."[8]
Pharmacogenomics
Heart failure
Regarding the treatment of heart failure, there is conflicting evidence whether adrenergic beta-antagonists are as effective in African-American patients as in Anglo patients.[9] This may be due to a polymorphism in African-American patients of the G protein–coupled cell surface receptor kinase 5 (GRK5) that confers a natural "genetic beta-blockade".[10][11]
G protein–coupled cell surface receptor kinase 2 (GRK2) genetic polymorphisms may also affect the response to adrenergic beta-antagonists.[12]
Asthma
Genetic polymorphisms may affect the response to adrenergic beta-antagonists by patients of African descent.[13]
References
- ↑ Anonymous (2024), G-protein-coupled receptor kinase (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 600870. World Wide Web URL: http://omim.org/.
- ↑ Lodish, Harvey F. (1999). “20.1. Overview of Extracellular Signaling”, Molecular cell biology. New York: Scientific American Books. ISBN 0-7167-3136-3.
- ↑ Anonymous (2024), G-protein-coupled receptor kinase 1 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), G-protein-coupled receptor kinase 2 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), G-protein-coupled receptor kinase 3 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), G-protein-coupled receptor kinase 4 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), G-protein-coupled receptor kinase 5 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Shekelle PG, Rich MW, Morton SC, et al (2003). "Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials". J. Am. Coll. Cardiol. 41 (9): 1529–38. PMID 12742294. [e]
- ↑ Liggett SB, Cresci S, Kelly RJ, et al. (May 2008). "A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure". Nat. Med. 14 (5): 510–7. DOI:10.1038/nm1750. PMID 18425130. PMC 2596476. Research Blogging.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 600870. World Wide Web URL: http://omim.org/.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 109635. World Wide Web URL: http://omim.org/.
- ↑ Wang WC, Mihlbachler KA, Bleecker ER, Weiss ST, Liggett SB (August 2008). "A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted desensitization of beta2-adrenergic receptors". Pharmacogenet. Genomics 18 (8): 729–32. DOI:10.1097/FPC.0b013e32830967e9. PMID 18622265. Research Blogging.