HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ulianich, L. Articles by Kohn, L. D. Search for Related Content PubMed PubMed Citation Articles by Ulianich, L. Articles by Kohn, L. D. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 35, 25099-25107, August 27, 1999

Follicular Thyroglobulin (TG) Suppression of Thyroid-restricted Genes Involves the Apical Membrane Asialoglycoprotein Receptor and TG Phosphorylation

Luca Ulianich^§, Koichi Suzuki, Atsumi Mori, Minoru Nakazato, Michele Pietrarelli, Paul Goldsmith, Francesco Pacifico^§, Eduardo Consiglio^§, Silvestro Formisano^§, and Leonard D. Kohn

From the  Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 and ^§ Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche and Dipartmento di Biologia e Patologia Cellulare e Moleculare "L. Califano," Federico II Medical School, Naples 80131, Italy

Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes (Suzuki, K., Lavaroni, S., Mori, A., Ohta, M., Saito, J., Pietrarelli, M., Singer, D. S., Kimura, S., Katoh, R., Kawaoi, A., and Kohn, L. D. (1997) Proc. Natl. Acad. Sci. U. S. A. 95, 8251-8256). The ability of highly purified 27, 19, or 12 S follicular TG to suppress thyroid-restricted gene expression correlates with their ability to bind to FRTL-5 thyrocytes and is inhibited by a specific antibody to the thyroid apical membrane asialoglycoprotein receptor (ASGPR), which is related to the ASGPR of liver cells. Phosphorylating serine/threonine residues of TG, by autophosphorylation or protein kinase A, eliminates TG suppression and enhances transcript levels of the thyroid-restricted genes 2-fold in the absence of a change in TG binding to the ASGPR. Follicular TG suppression of thyroid-restricted genes is thus mediated by the ASPGR on the thyrocyte apical membrane and regulated by a signal system wherein phosphorylation of serine/threonine residues on the bound ligand is an important component. These data provide a hitherto unsuspected role for the ASGPR in transcriptional signaling, aside from its role in endocytosis. They establish a functional role for phosphorylated serine/threonine residues on the TG molecule.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				G. Riesco-Eizaguirre and P. Santisteban A perspective view of sodium iodide symporter research and its clinical implications. Eur. J. Endocrinol., October 1, 2006; 155(4): 495 - 512. [Abstract] [Full Text] [PDF]

				K. Suzuki and L. D Kohn Differential regulation of apical and basal iodide transporters in the thyroid by thyroglobulin. J. Endocrinol., May 1, 2006; 189(2): 247 - 255. [Abstract] [Full Text] [PDF]

				O. Dohan, A. De la Vieja, V. Paroder, C. Riedel, M. Artani, M. Reed, C. S. Ginter, and N. Carrasco The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance Endocr. Rev., February 1, 2003; 24(1): 48 - 77. [Abstract] [Full Text] [PDF]

				B. Saunier, M. Triyatni, L. Ulianich, P. Maruvada, P. Yen, and L. D. Kohn Role of the Asialoglycoprotein Receptor in Binding and Entry of Hepatitis C Virus Structural Proteins in Cultured Human Hepatocytes J. Virol., December 6, 2002; 77(1): 546 - 559. [Abstract] [Full Text] [PDF]

				M. Nakazato, H.-K. Chung, L. Ulianich, A. Grassadonia, K. Suzuki, and L. D. Kohn Thyroglobulin Repression of Thyroid Transcription Factor 1 (TTF-1) Gene Expression Is Mediated by Decreased DNA Binding of Nuclear Factor I Proteins Which Control Constitutive TTF-1 Expression Mol. Cell. Biol., November 15, 2000; 20(22): 8499 - 8512. [Abstract] [Full Text]

				M. Marino and R. T. McCluskey Role of thyroglobulin endocytic pathways in the control of thyroid hormone release Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1295 - C1306. [Abstract] [Full Text] [PDF]

				F. Schuppert, D. Ehrenthal, A. Frilling, K. Suzuki, G. Napolitano, and L. D. Kohn Increased Major Histocompatibility Complex (MHC) Expression in Nontoxic Goiters Is Associated with Iodide Depletion, Enhanced Ability of the Follicular Thyroglobulin to Increase MHC Gene Expression, and Thyroid Autoantibodies J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 858 - 867. [Abstract] [Full Text]

				I. E. Royaux, K. Suzuki, A. Mori, R. Katoh, L. A. Everett, L. D. Kohn, and E. D. Green Pendrin, the Protein Encoded by the Pendred Syndrome Gene (PDS), Is an Apical Porter of Iodide in the Thyroid and Is Regulated by Thyroglobulin in FRTL-5 Cells Endocrinology, February 1, 2000; 141(2): 839 - 845. [Abstract] [Full Text] [PDF]

				K. Suzuki, A. Mori, J. Saito, E. Moriyama, L. Ullianich, and L. D. Kohn Follicular Thyroglobulin Suppresses Iodide Uptake by Suppressing Expression of the Sodium/Iodide Symporter Gene Endocrinology, November 1, 1999; 140(11): 5422 - 5430. [Abstract] [Full Text]