Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 504-513 |
| Number of pages | 10 |
| Journal | EMBO Journal |
| Volume | 21 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 15 2002 |
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Keywords
- Glycoprotein
- GPCR
- Hormones
- Sulfation
- Tyrosine
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors. / Costagliola, S.; Panneels, V.; Bonomi, M.; Koch, J.; Many, M. C.; Smits, G.; Vassart, G.
In: EMBO Journal, Vol. 21, No. 4, 15.02.2002, p. 504-513.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors
AU - Costagliola, S.
AU - Panneels, V.
AU - Bonomi, M.
AU - Koch, J.
AU - Many, M. C.
AU - Smits, G.
AU - Vassart, G.
PY - 2002/2/15
Y1 - 2002/2/15
N2 - 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.
AB - 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.
KW - Glycoprotein
KW - GPCR
KW - Hormones
KW - Sulfation
KW - Tyrosine
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UR - http://www.scopus.com/inward/citedby.url?scp=0037084011&partnerID=8YFLogxK
U2 - 10.1093/emboj/21.4.504
DO - 10.1093/emboj/21.4.504
M3 - Article
C2 - 11847099
AN - SCOPUS:0037084011
VL - 21
SP - 504
EP - 513
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 4
ER -