This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Métayé, T. Articles by Kraimps, J.-L. Search for Related Content PubMed PubMed Citation Articles by Métayé, T. Articles by Kraimps, J.-L.

Expression and Activity of G Protein-Coupled Receptor Kinases in Differentiated Thyroid Carcinoma

Biophysics Laboratory (T.M.), Department of Pathology (E.M.), Biostatistics Unit of Department of Hematology (J.G.), and Department of Endocrine Surgery (J.-L.K.), Jean Bernard Hospital, Groupe de Recherche en Endocrinologie Experimentale et Clinique, 86021 Poitiers Cedex, France

Address all correspondence and requests for reprints to: Thierry Métayé, Laboratoire de Biophysique, Hôpital Jean Bernard, BP 577, 86021 Poitiers Cedex, France. E-mail: . t.metaye{at}chu-poitiers.fr

Abstract

Most of the TSH effects on the proliferation and differentiation of thyroid cells are mediated by cAMP via an adenylyl cyclase-activating Gs protein. TSH receptor responsiveness in cell cultures, is regulated by G protein-coupled receptor kinase (GRK) 2 and 5. To determine whether an alteration in activity and expression of GRKs might be associated with variable levels of TSH receptor desensitization in vivo, we studied human thyroid tissues including 21 normal tissues and 18 differentiated carcinomas. GRK activity was assayed by rhodopsin phosphorylation, and GRK protein and mRNA expressions assessed by immunoblotting and real-time quantitative RT-PCR, respectively. GRK2 and GRK5 were found as the predominant isoforms in the human thyroid. GRK5 protein expression was significantly decreased in differentiated thyroid carcinoma (P < 0.02) and paralleled a decrease in GRK mRNA expression (P < 0.02). In contrast, no difference in protein and mRNA levels of GRK2 were observed between normal and cancerous thyroid tissues. Although GRK2 protein levels correlated with GRK activities, we demonstrated a significant increase in GRK activity in differentiated thyroid carcinoma (P < 0.02). Less TSH receptor desensitization occurred in differentiated carcinoma than in normal thyroid tissue, as judged by TSH-stimulated cAMP response in human thyroid cells in primary culture. In conclusion, this study indicates that GRK2 activity and GRK5 expression have opposite regulations in cancer cells. Furthermore, the decrease in GRK5 expression may underlie the reduction in homologous desensitization of the TSH receptor in differentiated thyroid carcinoma, contributing to explain the increased cAMP levels in these tumors.

This article has been cited by other articles:

				T. Metaye, P. Levillain, J.-L. Kraimps, and R. Perdrisot Immunohistochemical detection, regulation and antiproliferative function of G-protein-coupled receptor kinase 2 in thyroid carcinomas J. Endocrinol., July 1, 2008; 198(1): 101 - 110. [Abstract] [Full Text] [PDF]

				H.-Y. Zhang, H.-Q. Wang, H.-M. Liu, Y. Guan, and Z.-X. Du Regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by DJ-1 in thyroid cancer cells Endocr. Relat. Cancer, June 1, 2008; 15(2): 535 - 544. [Abstract] [Full Text] [PDF]

				V. Giroux, J. Iovanna, and J.-C. Dagorn Probing the human kinome for kinases involved in pancreatic cancer cell survival and gemcitabine resistance FASEB J, October 1, 2006; 20(12): 1982 - 1991. [Abstract] [Full Text] [PDF]