Methods to identify growth differentiation factor (GDF) receptors
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a growth differentiation factor and receptor technology, applied in the field of transforming growth factor . beta, can solve problems such as binding agents' interferen
Inactive Publication Date: 2004-04-22
THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
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Such binding agents may interfere by competitive inhibition,
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[0100] Distribution of Receptors for GDF-8 and GDF-11.
[0101] The purified GDF-8 and GDF-11 proteins will be used primarily to assay for biological activities. In order to identify potential target cells for GDF-8 and GDF-11 action cells expressing their receptors will be searched. For this purpose, the purified protein will be radioiodinated using the chloramine T method, which has been used successfully to label other members of this superfamily, like TGF-.beta. (Cheifetz et al., 1987), activins (Sugino et al., 1988), and BMPs (Paralkar et al., 1991), for receptor-binding studies. The mature processed forms of GDF-8 and GDF-11 each contain multiple tyrosine residues. Two different approaches will then be taken to attempt to identify receptors for these proteins.
[0102] One approach will be taken to determine the number, affinity, and distribution of receptors. Either whole cells grown in culture, frozen sections of embryos or adult tissues, or total membrane fractions prepared from ...
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Abstract
The present invention provides receptors for the growth differentiation factor (GDF) family of growth factors and methods of identifying such receptors. Also included are methods of identifying antibodies which bind to the receptors, peptide fragments of the receptor which inhibit GDF binding, GDF receptor-binding agents capable of blocking GDF binding to the receptor. The receptors of the invention allow the identification of antagonists or agonists useful for agricultural and human therapeutic purposes.
Description
[0001] This invention relates generally to ligand-receptor interactions and more specifically to growth differentiation factor receptor proteins and the ligands that bind to such receptors and methods of use therefor.DESCRIPTION OF RELATED ART[0002] The transforming growth factor .beta. (TGF-.beta.) superfamily encompasses a group of structurally-related proteins which affect a wide range of differentiation processes during embryonic development. The family includes, Mullerian inhibiting substance (MIS), which is required for normal male sex development (Behringer, et al., Nature, 345:167, 1990), Drosophila decapentaplegic (DPP) gene product, which is required for dorsal-ventral axis formation and morphogenesis of the imaginal disks (Padgett, et al., Nature, 325:81-84, 1987), the Xenopus Vg-1 gene product, which localizes to the vegetal pole of eggs ((Weeks, et al., Cell, 51:861-867, 1987), the activins (Mason, et al., Biochem, Biophys. Res. Commun., 135:957-964,1986), which can ind...
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