The goal of this proposal is to study the activation mechanism of the FSH receptor (FSH-R).
In Aim 1, the C-terminal residues of the FSH-a subunit will be examined to determine conclusively which amino acid(s) is involved in receptor activation, which might be involved in receptor binding, and what the structural and functional relationships of these amino acids are.
In Aim 2, the C-terminal half of the FSH-R will be investigated to identify the amino acid residues that are responsible for receptor activation and to determine their roles in receptor activation.
In Aim 3, the high affinity hormone contact points in the N-terminal half will be identified and the role of amino acids in hormone binding determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
7R01DK051469-04
Application #
2905878
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Sato, Sheryl M
Project Start
1996-09-15
Project End
2000-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Ji, Inhae; Lee, ChangWoo; Jeoung, MyoungKun et al. (2004) Trans-activation of mutant follicle-stimulating hormone receptors selectively generates only one of two hormone signals. Mol Endocrinol 18:968-78
Ko, CheMyong; Grieshaber, Nicole A; Ji, Inhae et al. (2003) Follicle-stimulating hormone suppresses cytosolic 3,5,3'-triiodothyronine-binding protein messenger ribonucleic acid expression in rat granulosa cells. Endocrinology 144:2360-7
Grieshaber, Nicole A; Ko, CheMyong; Grieshaber, Scott S et al. (2003) Follicle-stimulating hormone-responsive cytoskeletal genes in rat granulosa cells: class I beta-tubulin, tropomyosin-4, and kinesin heavy chain. Endocrinology 144:29-39
Sohn, Johann; Youn, HyeSook; Jeoung, MyoungKun et al. (2003) Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3. J Biol Chem 278:47868-76
Ji, Inhae; Lee, ChangWoo; Song, YongSang et al. (2002) Cis- and trans-activation of hormone receptors: the LH receptor. Mol Endocrinol 16:1299-308
Bozon, Veronique; Couture, Laurence; Pajot-Augy, Edith et al. (2002) Rescue of intracellularly trapped lutropin receptor exodomain by endodomain and reconstitution of a functional membrane receptor: interaction between exo- and endodomains. Protein Expr Purif 25:114-23
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Lee, ChangWoo; Ji, Inhae Ji; Ji, Tae H (2002) Use of defined-function mutants to access receptor-receptor interactions. Methods 27:318-23
Lee, ChangWoo; Ji, Inhae; Ryu, KiSung et al. (2002) Two defective heterozygous luteinizing hormone receptors can rescue hormone action. J Biol Chem 277:15795-800
Sohn, Johann; Ryu, KiSung; Sievert, Gail et al. (2002) Follicle-stimulating hormone interacts with exoloop 3 of the receptor. J Biol Chem 277:50165-75

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