The glycoprotein hormone receptors (thyrotrophin receptor, TSHr; luteinizing hormone/chorionic gonadotrophin receptor, LH/CGr; follicle-stimulating hormone receptor, FSHr) constitute a subfamily of rhodopsin-like G protein-coupled receptors (GPCRs) with a long N-terminal extracellular extension responsible for high-affinity hormone binding. These ectodomains contain two cysteine clusters flanking nine leucine-rich repeats (LRR), a motif found in several protein families involved in protein-protein interactions. Similar to the situation described recently in CCR5, we demonstrate here that the TSHr, as it is present at the cell surface, is sulfated on tyrosines in a motif located downstream of the C-terminal cysteine cluster. Sulfation of one of the two tyrosines in the motif is mandatory for high-affinity binding of TSH and activation of the receptor. Site-directed mutagenesis experiments indicate that the motif, which is conserved in all members of the glycoprotein hormone receptor family, seems to play a similar role in the LH/CG and FSH receptors.
Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors / S. Costagliola, V. Panneels, M. Bonomi, J. Koch, M. Many, G. Smits, G. Vassart. - In: EMBO JOURNAL. - ISSN 0261-4189. - 21:4(2002 Feb 15), pp. 504-513.
|Titolo:||Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||15-feb-2002|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/emboj/21.4.504|
|Appare nelle tipologie:||01 - Articolo su periodico|