Abstract

The current proposal seeks to define the impact of FSHR phosphorylation on the functions of FSHR, and to further understand the mechanisms involved in phosphorylation. Specifically, it is proposed to: 1) use site-directed mutagenesis to identify the amino acid residues which are phosphorylated in response to FSH and PMA and to examine the functional consequences of FSH- and PMA-induced FSHR phosphorylation; and 2) identify the protein kinases that phosphorylate the FSHR. By analogy with the beta adrenergic receptor, it is reasonable to propose that phosphorylation of the FSHR may be involved in the termination of the actions of FSH and in the regulation of the functions of FSHR by other hormones. In the face of constant hormone levels, a lack of regulation at the level of the receptor would result in hyperstimulation of the target cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028962-07
Application #
2889054
Study Section
Endocrinology Study Section (END)
Program Officer
Yoshinaga, Koji
Project Start
1992-04-01
Project End
2000-04-05
Budget Start
1999-04-01
Budget End
2000-04-05
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

Andric, Nebojsa; Thomas, Mika; Ascoli, Mario (2010) Transactivation of the epidermal growth factor receptor is involved in the lutropin receptor-mediated down-regulation of ovarian aromatase expression in vivo. Mol Endocrinol 24:552-60
Andric, Nebojsa; Ascoli, Mario (2008) Mutations of the lutropin/choriogonadotropin receptor that do not activate the phosphoinositide cascade allow hCG to induce aromatase expression in immature rat granulosa cells. Mol Cell Endocrinol 285:62-72
Andric, Nebojsa; Ascoli, Mario (2008) The luteinizing hormone receptor-activated extracellularly regulated kinase-1/2 cascade stimulates epiregulin release from granulosa cells. Endocrinology 149:5549-56
Andric, Nebojsa; Ascoli, Mario (2006) A delayed gonadotropin-dependent and growth factor-mediated activation of the extracellular signal-regulated kinase 1/2 cascade negatively regulates aromatase expression in granulosa cells. Mol Endocrinol 20:3308-20
Bhaskaran, R S; Ascoli, M (2005) The post-endocytotic fate of the gonadotropin receptors is an important determinant of the desensitization of gonadotropin responses. J Mol Endocrinol 34:447-57
Donadeu, Francesc Xavier; Ascoli, Mario (2005) The differential effects of the gonadotropin receptors on aromatase expression in primary cultures of immature rat granulosa cells are highly dependent on the density of receptors expressed and the activation of the inositol phosphate cascade. Endocrinology 146:3907-16
Krishnamurthy, Hanumanthappa; Kishi, Hiroshi; Shi, Mei et al. (2003) Postendocytotic trafficking of the follicle-stimulating hormone (FSH)-FSH receptor complex. Mol Endocrinol 17:2162-76
Bhaskaran, Ravi Sankar; Min, Le; Krishnamurthy, Hanumanthappa et al. (2003) Studies with chimeras of the gonadotropin receptors reveal the importance of third intracellular loop threonines on the formation of the receptor/nonvisual arrestin complex. Biochemistry 42:13950-9
Krishnamurthy, Hanumanthappa; Galet, Colette; Ascoli, Mario (2003) The association of arrestin-3 with the follitropin receptor depends on receptor activation and phosphorylation. Mol Cell Endocrinol 204:127-40
Kishi, Hiroshi; Krishnamurthy, Hanumanthappa; Galet, Colette et al. (2002) Identification of a short linear sequence present in the C-terminal tail of the rat follitropin receptor that modulates arrestin-3 binding in a phosphorylation-independent fashion. J Biol Chem 277:21939-46

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