Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors

EMBO J. 2002 Feb 15;21(4):504-13. doi: 10.1093/emboj/21.4.504.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Autoantibodies / immunology
  • Epitopes / chemistry
  • Humans
  • Immunohistochemistry
  • Molecular Sequence Data
  • Receptors, Cell Surface / agonists*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Sequence Homology, Amino Acid
  • Sulfuric Acids / metabolism*
  • Tyrosine / metabolism*


  • Antibodies, Monoclonal
  • Autoantibodies
  • Epitopes
  • Receptors, Cell Surface
  • Sulfuric Acids
  • Tyrosine