Penela P, Barradas M, Alvarez-Dolado M, Muñoz A, Mayor F
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa , Universidad Autónoma, 28049 Madrid, Spain.
Endocrinology. 2001 Mar;142(3):987-91. doi: 10.1210/endo.142.3.8039.
GRK2 is a member of the G protein-coupled receptor kinase family that phosphorylates the activated form of beta-adrenergic and other G protein-coupled receptors and plays an important role in their desensitization and modulation. Alterations in thyroid hormone levels have been reported to lead to important changes in adrenergic receptor responsiveness and signaling in a variety of tissues. In this context, we have explored the effects of experimental hypothyroidism on GRK2 protein levels in rat heart, lung, and liver using a specific antibody. Hypothyroid animals show significant up-regulation ( approximately 50% increase compared with controls) in GRK2 levels in heart and lung at 60 days after birth, whereas a 50% reduction is detected in the liver at this stage. These alterations are selective, as beta-adrenergic receptors or other G protein-coupled receptor regulatory proteins, such as G protein-coupled receptor kinase 5 or beta-arrestin-1, display a different pattern of expression changes in the hypothyroid animals. The reported changes in GRK2 levels and in the receptor/kinase ratio predict alterations in adrenergic receptor desensitization and signal transduction efficacy consistent with those observed in thyroid disorders, thus suggesting a relevant role for the modulation of GRK2 expression in this physiopathological condition.
GRK2是G蛋白偶联受体激酶家族的成员，它使β-肾上腺素能受体和其他G蛋白偶联受体的激活形式磷酸化，并在其脱敏和调节过程中发挥重要作用。据报道，甲状腺激素水平的改变会导致多种组织中肾上腺素能受体反应性和信号传导的重要变化。在此背景下，我们使用特异性抗体研究了实验性甲状腺功能减退对大鼠心脏、肺和肝脏中GRK2蛋白水平的影响。出生60天后，甲状腺功能减退的动物心脏和肺中的GRK2水平显著上调（与对照组相比增加约50%），而在此阶段肝脏中GRK2水平则降低50%。这些改变具有选择性，因为β-肾上腺素能受体或其他G蛋白偶联受体调节蛋白，如G蛋白偶联受体激酶5或β-抑制蛋白-1，在甲状腺功能减退的动物中表现出不同的表达变化模式。报道的GRK2水平和受体/激酶比值的变化预示着肾上腺素能受体脱敏和信号转导效率的改变，这与甲状腺疾病中观察到的情况一致，因此表明GRK2表达的调节在这种生理病理状态中具有重要作用。
