Why the study?
Does cardiac-specific overexpression of GRK5 cause selective receptor desensitization in transgenic mice?
Does cardiac-specific overexpression of GRK5 cause selective receptor desensitization in transgenic mice?
Myocardial overexpression of GRK5 results in selective uncoupling of G protein-coupled receptors, demonstrating that receptor specificity of GRKs may determine physiological phenotype.
GRK5 selectively desensitizes beta-receptors in mice; leaves open whether GRK specificity shapes human HF phenotypes.
Transgenic mice were generated with cardiac-specific overexpression of the G protein-coupled receptor kinase-5 (GRK5), a serine/threonine kinase most abundantly expressed in the heart compared with other tissues. Animals overexpressing GRK5 showed marked beta-adrenergic receptor desensitization in both the anesthetized and conscious state compared with nontransgenic control mice, while the contractile response to angiotensin II receptor stimulation was unchanged. In contrast, the angiotensin II-induced rise in contractility was significantly attenuated in transgenic mice overexpressing the beta-adrenergic receptor kinase-1, another member of the GRK family. These data suggest that myocardial overexpression of GRK5 results in selective uncoupling of G protein-coupled receptors and demonstrate that receptor specificity of the GRKs may be important in determining the physiological phenotype.
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Rockman et al. (1996) studied this question.