G-protein-coupled receptor kinase: Difference between revisions
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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> | 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. | 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=== | ===Asthma=== | ||
Revision as of 08:15, 29 August 2009
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.