This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Chazenbalk, G. D. Articles by Rapoport, B. Search for Related Content PubMed PubMed Citation Articles by Chazenbalk, G. D. Articles by Rapoport, B.

Signal Transduction by the Human Thyrotropin Receptor: Studies on the Role of Individual Amino Acid Residues in the Carboxyl Terminal Region of the Third Cytoplasmic Loop

Thyroid Molecular Biology Unit, Veterans Administration Medical Center, University of California San Francisco, California 94121

Address requests for reprints to: Gregorio Chazenbalk, Ph.D., Veterans Administration Medical Center, Thyroid Molecular Biology Unit (111T), 4150 Clement Street, San Francisco, California 94121.

Abstract

We observed previously that the carboxyl-terminal region of the third loop of the TSH receptor (amino acid residues 617–625) is important in signal transduction. To analyze this region in more detail, in the present study we used site-directed mutagenesis to substitute, on an individual basis, the seven amino acids previously mutated as a group. These amino acids are either charged residues or potential phosphorylation sites. Six of the mutant TSH receptors with individual amino acid substitutions bound TSH with high affinity and displayed a cAMP response to TSH stimulation similar to the wild-type TSH receptor. The mutant receptor TSH-R-Gly⁶²⁵ (Arg Gly) did not transduce a signal, but these results are noninformative because of the loss of high affinity TSH binding. The present data indicate that for each of the six informative amino acid substitutions, the individual residues are not critical for signal transduction. A corollary of this conclusion is that in the important carboxyl-terminal region of the third cytoplasmic loop of the TSH receptor multiple amino acid residues function as a unit.

FOOTNOTES

This work was supported by NIH Grants DK-19289 and DK-36182, and the Research Service of the V.A.

Received for publication May 10, 1991. Revision received July 25, 1991. Accepted for publication July 25, 1991.

This article has been cited by other articles:

				P. Wonerow, T. Schoneberg, G. Schultz, T. Gudermann, and R. Paschke Deletions in the Third Intracellular Loop of the Thyrotropin Receptor. A NEW MECHANISM FOR CONSTITUTIVE ACTIVATION J. Biol. Chem., April 3, 1998; 273(14): 7900 - 7905. [Abstract] [Full Text] [PDF]

				A. Schulz, K. Bruns, P. Henklein, G. Krause, M. Schubert, T. Gudermann, V. Wray, G. Schultz, and T. Schoneberg Requirement of Specific Intrahelical Interactions for Stabilizing the Inactive Conformation of Glycoprotein Hormone Receptors J. Biol. Chem., November 22, 2000; 275(48): 37860 - 37869. [Abstract] [Full Text] [PDF]