Rockman H A, Choi D J, Rahman N U, Akhter S A, Lefkowitz R J, Koch W J
Department of Medicine, University of California San Diego School of Medicine, La Jolla 92093, USA.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9954-9. doi: 10.1073/pnas.93.18.9954.
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.
通过心脏特异性过表达G蛋白偶联受体激酶5（GRK5）生成了转基因小鼠，GRK5是一种丝氨酸/苏氨酸激酶，与其他组织相比，在心脏中表达最为丰富。与非转基因对照小鼠相比，过表达GRK5的动物在麻醉和清醒状态下均表现出明显的β-肾上腺素能受体脱敏，而对血管紧张素II受体刺激的收缩反应未发生变化。相比之下，在过表达β-肾上腺素能受体激酶-1（GRK家族的另一个成员）的转基因小鼠中，血管紧张素II诱导的收缩力增加显著减弱。这些数据表明，GRK5在心肌中的过表达导致G蛋白偶联受体的选择性解偶联，并证明GRK的受体特异性在决定生理表型方面可能很重要。
