+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Yoked complexes of human choriogonadotropin and the lutropin receptor: evidence that monomeric individual subunits are inactive



Yoked complexes of human choriogonadotropin and the lutropin receptor: evidence that monomeric individual subunits are inactive



Molecular Endocrinology 16(12): 2733-2745



Human choriogonadotropin (hCG) contains an alpha-subunit, common to other members of the glycoprotein hormone family, and a unique beta-subunit that determines hormone specificity. It is generally thought that heterodimer formation is obligatory for full hormonal activity, although other studies have indicated that individual subunits and homodimeric hCGbeta were capable of low affinity binding to the LH receptor (LHR) and subsequent activation. Previously, we constructed two yoked hormone (hCG)-LHR complexes, where the two hormone subunits and the heptahelical receptor were engineered to form single polypeptide chains, i.e. N-beta-alpha-LHR-C and N-alpha-beta-LHR-C. Expression of both complexes led to constitutive stimulation of cAMP production. In the present study, we investigated whether the human alpha-subunit and hCGbeta can act as functional agonists when covalently attached to or coexpressed with the LH receptor. Our initial results showed that hCGbeta, but not alpha, was able to activate LHR with an increase in intracellular cAMP in human embryonic kidney 293 cells but not in Chinese hamster ovary or COS-7 cells. Further examination of this apparent cell-specific agonist activity of hCGbeta revealed that low levels of endogenous alpha-subunit were expressed in human embryonic kidney 293 cells, thus enabling sufficient amounts of active heterodimer to form with the transfected hCGbeta to activate LHR. The studies in Chinese hamster ovary and COS-7 cells clearly demonstrate that, even under experimental conditions where hormone-receptor interactions are maximized, individual subunits of hCG can not act as functional agonists, at least in their monomeric form.

(PDF emailed within 0-6 h: $19.90)

Accession: 011659310

Download citation: RISBibTeXText

PMID: 12456794

DOI: 10.1210/me.2002-0208


Related references

The role of Asp578 in maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor. Journal of Biological Chemistry 271(50): 31813-7, 1996

An anionic residue at position 564 is important for maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor. Molecular Pharmacology 53(5): 894-901, 1998

A defined epitope on the human choriogonadotropin a-subunit interacts with the second extracellular loop of the transmembrane domain of the lutropin/choriogonadotropin receptor. European Journal of Biochemistry 241: 7-32, 1996

Deletions of portions of the extracellular loops of the lutropin/choriogonadotropin receptor decrease the binding affinity for ovine luteinizing hormone, but not human choriogonadotropin, by preventing the formation of mature cell surface receptor. Journal of Biological Chemistry 271(8): 4518-4527, 1996

A defined epitope on the human choriogonadotropin alpha-subunit interacts with the second extracellular loop of the transmembrane domain of the lutropin/choriogonadotropin receptor. European Journal of Biochemistry 241(2): 627-632, 1996

Beta subunits of human choriogonadotropin and ovine lutropin are biologically active. Proceedings of the National Academy of Sciences of the United States of America 79(8): 2500-2503, 1982

Association of human follitropin (FSH) receptor with splicing variant of human lutropin/choriogonadotropin receptor negatively controls the expression of human FSH receptor. Molecular Endocrinology 19(8): 2099-2111, 2005

Extracellular domain of lutropin/choriogonadotropin receptor expressed in transfected cells binds choriogonadotropin with high affinity. Journal of Biological Chemistry 265(35): 21411-4, 1990

The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor contacts both subunits of human choriogonadotropin. II. Photoaffinity labeling. Journal of Biological Chemistry 273(22): 13841-7, 1998

The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor contacts both subunits of human choriogonadotropin. I. Mutational analysis. Journal of Biological Chemistry 273(22): 13835-13840, 1998

Evidence for the direct involvement of transmembrane region 6 of the lutropin/choriogonadotropin receptor in activating Gs. Journal of Biological Chemistry 272(23): 14586-14591, 1997

The association of arrestin-3 with the human lutropin/choriogonadotropin receptor depends mostly on receptor activation rather than on receptor phosphorylation. Journal of Biological Chemistry 277(1): 702-710, 2001

Structural homologies in the lutropin/human choriogonadotropin receptor and the follitropin receptor on porcine granulosa cells. Biochemistry 25(11): 3410-3415, 1986

Desensitization of Gs-coupled receptor signaling by constitutively active mutants of the human lutropin/choriogonadotropin receptor. Journal of Clinical Endocrinology and Metabolism 88(3): 1194-1204, 2003