Agonist-stimulated internalization of the thyrotropin-releasing hormone receptor is dependent on two domains in the receptor carboxyl terminus

Daniel R. Nussenzveig, Marcos Heinflink, Marvin C. Gershengorn

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

The thyrotropin-releasing hormone (TRH)-TRH receptor (TRHR) complex undergoes rapid transformation in cells to an acid-resistant form which appears to represent internalized agonist-receptor complex. Since residues in the carboxyl terminus of other G protein-coupled receptors appear to be involved in internalization, we studied the role of this domain in the TRHR. A mutant TRHR, C335Stop, missing the last 59 residues including 2 cysteine residues, undergoes minimal transformation to an acid-resistant form even though it binds agonist with equal affinity and activates inositol phosphate second messenger formation as effectively as wild type TRHR. Two distinct domains within the carboxyl terminus between residues 335 and 368 were shown to affect transformation equally. First, a domain between residues 360 and 367 was identified because a TRHR with codon 360 mutated to a stop codon attained a steady-state level of internalized receptor that was approximately 50% of wild type TRHR, whereas a mutant with codon 368 changed to a stop was internalized to the same extent as wild type TRHR. Second, the need for a proximal Cys residue(s), Cys-335 or Cys-337, was shown by mutating these residues to Ser or Gly. We conclude that rapid internalization of the TRHR is dependent on two dissimilar domains within the receptor carboxyl terminus.

Original languageEnglish (US)
Pages (from-to)2389-2392
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number4
StatePublished - Feb 5 1993

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Thyrotropin Releasing Hormone Receptors
Codon
Acids
Inositol Phosphates
Thyrotropin-Releasing Hormone
Terminator Codon
Second Messenger Systems
G-Protein-Coupled Receptors
Cysteine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Agonist-stimulated internalization of the thyrotropin-releasing hormone receptor is dependent on two domains in the receptor carboxyl terminus. / Nussenzveig, Daniel R.; Heinflink, Marcos; Gershengorn, Marvin C.

In: Journal of Biological Chemistry, Vol. 268, No. 4, 05.02.1993, p. 2389-2392.

Research output: Contribution to journalArticle

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