Growth differentiation factor-10

Details Growth differentiation factor-10 Growth differentiation factor-10

1996-10-10

2001-03-20

Walsh, Stephen (Department: 1812)

Chemistry: molecular biology and microbiology

Micro-organism, per se ; compositions thereof; proces of...

Bacteria or actinomycetales; media therefor

C435S320100, C530S399000, C536S023500

Reexamination Certificate

active

06204047

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates generally to growth factors and specifically to a new member of the transforming growth factor beta (TGF-&bgr;) superfamily, which is denoted, growth differentiation factor-10 (GDF-10).
2. Description of Related Art
The transforming growth factor &bgr; (TGF-&bgr;) 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: 1-84, 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 induce the formation of mesoderm and anterior structures in Xenopus embryos (Thomsen, et al.,
Cell,
63:485, 1990), and the bone morphogenetic proteins (BMPS, osteogenin, OP-1) which can induce de novo cartilage and bone formation (Sampath, et al.,
J. Biol. Chem.,
265:13198,1990). The TGF-&bgr;s can influence a variety of differentiation processes, including adipogenesis, myogenesis, chondrogenesis, hematopoiesis, and epithelial cell differentiation (for review, see Massague,
Cell
49:437, 1987).
The proteins of the TGF-&bgr; family are initially synthesized as a large precursor protein which subsequently undergoes proteolytic cleavage at a cluster of basic residues approximately 110-140 amino acids from the C-terminus. The C-terminal regions, or mat regions, of the proteins are all structurally related and the different family members can be classified into distinct subgroups based on the extent of their homology. Although the homologies within particular subgroups range from 70% to 90% amino acid sequence identity, the homologies between subgroups are significantly lower, generally ranging from only 20% to 50%. In each case, the active species appears to be a disulfide-linked dimer of C-terminal fragments. For most of the family members that have been studied, the homodimeric species has bee found to be biologically active, but for other family members, like he inhibins (Ling, et al.,
Nature,
321:779, 1986) and the TGF-&bgr;s (Cheifetz, et al.,
Cell,
48:409, 1987), heterodimers have also been detected, and these appear to have different biological properties than the respective homodimers.
Identification of new factors that are tissue-specific in their expression pattern will provide a greater understanding of that tissue's development and function and allow development of effective diagnostic and therapeutic regimens.
SUMMARY OF THE INVENTION
The present invention provides a cell growth and differentiation factor, GDF-10, a polynucleotide sequence which encodes the factor, and antibodies which are immunoreactive with the factor. This factor appears to relate to various cell proliferative disorders, especially those involving those involving uterine, nerve, bore, and adipose tissue.
Thus, in one embodiment, the invention provides a method for detecting a cell proliferative disorder of uterine, nerve, or fat origin and which is associated with GDF-10. In another embodiment, the invention provides a method for treating a cell proliferative disorder by suppressing or enhancing GDF-10 activity.


REFERENCES:
patent: 5468845 (1995-11-01), Oppermann et al.
patent: WO 94/01557 (1994-01-01), None
Wozney et al. Science 242, 1528-1534, 1988.*
S. Lee, Expression of growth/differentiation factor 1 in the nervous system: Conservation of a bicistronic structure,Proceedings of the National Academy of Sciences USA, vol. 88, May 1991, pp. 4250-4254.
Alexandra C. McPherron et al., GDF-3 and GDF-9: Two New Members of the Transforming Growth Factor-&bgr; Superfamily Containing a Novel Pattern of Cysteines*,Journal of Biological Chemistry, vol. 268, No. 5, Feb. 15, 1993, pp. 3444-3449.
C. Michael Jones et al., Isolation of Vgr-2, a Novel Member of the Transforming Growth Factor-&bgr;-Related Gene Family,Molecular Endocrinology, vol. 6, No. 11, 1992, pp. 1961-1968.
S. Lee, Identification of a Novel Member (GDF-1) of the Transforming Growth Factor-&bgr; Superfamily,Molecular Endocrinology, vol. 4, No. 7, 1990, pp. 1034-1039.

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