This research proposal will focus on the mechanism of desensitization of the human follicle stimulating hormone receptor (hFSHR) using novel approaches which have not yet been applied to this research problem. The long term objectives of this research are to understand the role of receptor desensitization and trafficking in the context of reproductive health, specifically in infertility and contraception.
The first aim i s to determine if receptor occupancy is required for desensitization by examining phosphorylation of FSHR in cells containing a mixed population of mutant hFSHR which cannot bind hormone and wild type hFSHR.
The second aim i s to identify in granulosa cells, which expresses hFSHR in vivo, which members of the family of G protein-coupled receptor kinases are present and responsible for phosphorylating hFSHR.
The final aim i s to use the yeast two-hybrid system to identify proteins which interact with the receptor. Using these three approaches will help to increase the understanding of what factors are required for proper receptor signaling and how that signal is terminated.
| Nechamen, Cheryl A; Thomas, Richard M; Cohen, Brian D et al. (2004) Human follicle-stimulating hormone (FSH) receptor interacts with the adaptor protein APPL1 in HEK 293 cells: potential involvement of the PI3K pathway in FSH signaling. Biol Reprod 71:629-36 |
| Cohen, Brian D; Nechamen, Cheryl A; Dias, James A (2004) Human follitropin receptor (FSHR) interacts with the adapter protein 14-3-3tau. Mol Cell Endocrinol 220:1-7 |
| Cohen, Brian D; Bariteau, Jason T; Magenis, Lori M et al. (2003) Regulation of follitropin receptor cell surface residency by the ubiquitin-proteasome pathway. Endocrinology 144:4393-402 |
| Dias, James A; Cohen, Brian D; Lindau-Shepard, Barbara et al. (2002) Molecular, structural, and cellular biology of follitropin and follitropin receptor. Vitam Horm 64:249-322 |
