Increased expression of G-protein-coupled receptor kinases 3 and 4 in hyperfunctioning thyroid nodules

The Journal of Endocrinology
Carsten VoigtRalf Paschke

Abstract

G-protein-coupled receptor kinases (GRKs) are implicated in the pathophysiology of human diseases such as arterial hypertension, heart failure and rheumatoid arthritis. While G-protein-coupled receptor kinases 2 and 5 have been shown to be involved in the desensitization of the rat thyrotropin receptor (TSHR), their role in the pathophysiology of hyperfunctioning thyroid nodules (HTNs) is unknown. Therefore, we analyzed the expression pattern of the known GRKs in human thyroid tissue and investigated their function in the pathology of HTNs. The expression of different GRKs in human thyroid and HTNs was measured by Western blotting. The influence of GRK expression on TSHR function was analyzed by coexpression experiments in HEK 293 cells. We demonstrate that in addition to GRKs 2, 5 and 6, GRKs 3 and 4 are also expressed in the human thyroid. GRKs 2, 3, 5 and 6 are able to desensitize the TSHR in vitro. This GRK-induced desensitization is amplified by the additional over-expression of beta-arrestin 1 or 2. We did not find any mutations in the GRKs 2, 3 and 5 from 14 HTNs without TSHR mutations and Gsalpha mutations. The expression of GRKs 3 and 4 was increased in HTNs independently from the existence of TSHR mutations or Gsalpha...Continue Reading

Citations

May 17, 2005·Cellular Signalling·Thierry MétayéJean-Louis Kraimps
Oct 12, 2010·European Journal of Endocrinology·A HébrantJ Leclère
Dec 31, 2005·Proceedings of the National Academy of Sciences of the United States of America·Wilma C G van StaverenCarine Maenhaut
May 25, 2011·The Journal of Infectious Diseases·Gerritje J W van der WindtTom van der Poll
May 26, 2007·Trends in Endocrinology and Metabolism : TEM·Romy Kursawe, Ralf Paschke
Oct 31, 2006·Biochimica Et Biophysica Acta·Regina AlemanyValentina Ruiz-Gutierrez
Dec 24, 2004·Endocrine Reviews·Knut KrohnRalf Paschke
Apr 3, 2015·Physiological Reviews·Priscila Y SatoWalter J Koch
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity·Markus EszlingerRalf Paschke
Apr 9, 2016·Oncotarget·Maria Carmela CantisaniMaria Domenica Castellone
Jan 5, 2007·World Journal of Gastroenterology : WJG·Wen Yang, Shi-Hai Xia

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