This Program Project focuses on the role of activins/inhibins and their binding proteins, receptors and downstream modulators in the regulation of reproductive function, cellular growth and development.
The first aim of this Program is to characterize the structure of activin-activin/receptor complexes and physical interactions between activin, its receptors and binding proteins, and downstream regulatory molecules.
The second aim i s to explore the physiologic and pathophysiologic significance of these molecules at the cellular and system levels and to study the control of protein expression and secretion as well as modes of action. These studies require high affinity, high titer antibodies of appropriate specificity for immunoprecipitation, immunoblot radioimmunoassay (RIA), Immunohistochemistry, and/or immunoneutralization techniques. This Core will produce and characterize polyclonal antisera needed by the immunoneutralization techniques. This Core will produce and characterize polyclonal antisera needed by the Projects of this Program to carry out structural, functional and mechanistic studies. We will use synthetic peptides conjugated to carrier proteins as immunogens to develop antibodies directed towards gene products predicted from the cDNA sequences or from amino acid sequencing of tryptic fragments of purified natural products. Alternatively, proteins produced using in vitro cell expression systems and provided by individual Projects will be injected directly into host animals for production of anti-sera. To reduce cross-reactivity with antigens other than the protein of interest, selected antisera will be immunoaffinity purified using the cognitive peptide, recombinant protein, or fusion protein covalently bound to an agarose- based gel. Physiologic and pharmacologic studies proposed by the Projects in this Program are critically dependent upon our ability to measure relevant hormones in a variety of biological fluids. The core will provide RIAs of pituitary gonadotropic hormones and sex steroids. The Core is responsible for ensuring quality control of these assays. The core will be under the overall responsibility of Drs. C. Rivier (RIA analysis of biological fluids, 10% effort) and W. Vale (antibody production, 3% effort). Day to day operation of the antisera production and purification component of Core B will be under the supervision of J. Vaughan (10% effort).
| Muenster, Uwe; Korupolu, Radhika; Rastogi, Ratindra et al. (2011) Antagonism of activin by activin chimeras. Vitam Horm 85:105-28 |
| Kim, Meejung; Choe, Senyon (2011) BMPs and their clinical potentials. BMB Rep 44:619-34 |
| Looyenga, Brendan D; Wiater, Ezra; Vale, Wylie et al. (2010) Inhibin-A antagonizes TGFbeta2 signaling by down-regulating cell surface expression of the TGFbeta coreceptor betaglycan. Mol Endocrinol 24:608-20 |
| Valera, Elvira; Isaacs, Michael J; Kawakami, Yasuhiko et al. (2010) BMP-2/6 heterodimer is more effective than BMP-2 or BMP-6 homodimers as inductor of differentiation of human embryonic stem cells. PLoS One 5:e11167 |
| Isaacs, Michael J; Kawakami, Yasuhiko; Allendorph, George P et al. (2010) Bone morphogenetic protein-2 and -6 heterodimer illustrates the nature of ligand-receptor assembly. Mol Endocrinol 24:1469-77 |
| Hassold, Terry; Hunt, Patricia (2009) Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew. Curr Opin Pediatr 21:703-8 |
| Wiater, Ezra; Lewis, Kathy A; Donaldson, Cynthia et al. (2009) Endogenous betaglycan is essential for high-potency inhibin antagonism in gonadotropes. Mol Endocrinol 23:1033-42 |
| Cheng, Edith Y; Hunt, Patricia A; Naluai-Cecchini, Theresa A et al. (2009) Meiotic recombination in human oocytes. PLoS Genet 5:e1000661 |
| Ciarmela, Pasquapina; Wiater, Ezra; Smith, Sean M et al. (2009) Presence, actions, and regulation of myostatin in rat uterus and myometrial cells. Endocrinology 150:906-14 |
| Blount, Amy L; Vaughan, Joan M; Vale, Wylie W et al. (2008) A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene. J Biol Chem 283:7016-26 |
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