Effect of hypothyroidism on G protein-coupled receptor kinase 2 expression levels in rat liver, lung, and heart.
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.
Penela
P
P
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa , Universidad Autónoma, 28049 Madrid, Spain.
Barradas
M
M
Alvarez-Dolado
M
M
Muñoz
A
A
Mayor
F
F
D000375:Aging / Q000378:metabolism; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D054769:G-Protein-Coupled Receptor Kinase 2; D007037:Hypothyroidism / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D051552:beta-Adrenergic Receptor Kinases
D017868:Cyclic AMP-Dependent Protein Kinases; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2