Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hansen, J.L. et al.

Role of G-protein-coupled receptor kinase 2 in the heart--do regulatory mechanisms open novel therapeutic perspectives?

G-protein-coupled receptor kinase ( GRK) 2 regulates a plethora of cellular processes, including cardiac expression and function of key seven-transmembrane receptors (7TM receptors) such as the beta-adrenergic and angiotensin receptors (Penela P, Murga C, Ribas C, et al.: 2006. Mechanisms of regulation of G-protein-coupled receptor kinases [GRKs] and cardiovascular disease. Cardiovasc Res 69:46-56, Rockman HA, Koch WJ, Lefkowitz RJ: 2002. Seven-transmembrane-spanning receptors and heart function. Nature 415:206-212). Interestingly, these two G-protein-coupled receptor systems are targeted by modern heart failure treatment including beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Although GRK2 is ubiquitously expressed, its particular importance in the heart has been demonstrated by interesting phenotypes of genetically altered mice that suggest GRK2 inhibition can ameliorate heart failure. In essence, this work suggests GRK2 could be an endogenous receptor blocker targeting both the beta-adrenergic and angiotensin receptors in the heart. This notion immediately suggests it is important to understand the molecular mechanisms that regulate GRK2 activity in the heart. In this review, we provide a detailed presentation of the tight regulation of GRK2 expression levels and protein activity, and we discuss the cardiovascular GRK2 functions and possible therapeutic perspectives.[1]

References

Role of G-protein-coupled receptor kinase 2 in the heart--do regulatory mechanisms open novel therapeutic perspectives? Hansen, J.L., Theilade, J., Aplin, M., Sheikh, S.P. Trends Cardiovasc. Med. (2006) [Pubmed]

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