Growth differentiation factor, lefty-2

Details Growth differentiation factor, lefty-2 Growth differentiation factor, lefty-2

2000-04-14

2003-10-21

Kemmerer, Elizabeth (Department: 1646)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

C435S252300, C435S320100, C530S350000, C530S351000, C530S387100, C530S387900, C530S388100, C530S389100, C536S023100, C536S023500

Reexamination Certificate

active

06635480

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 diferentiation factor, Lefty-2.
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,
325:81-84, 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 induce the formation of mosoderm and anterior structures in Xenopus embryos (Thomsen, et al.,
Cell,
63:485 1990), GDNF, which can promote the survival of motor neurons and midbrain dopaminergic neurons (Lin, et al.,
Science,
260:1130, 1993; Tomae, et al.,
Nature,
373:335, 1995; Beck, et al.,
Nature,
373:339, 1995; Henderson, et al.,
Science,
266:1062, 1994; Van, et al.,
Nature,
373:341, 1995; Oppenheim, et al.,
Nature,
373:344, 1995) 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 mature 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. Studies have shown that when the pro-region of a member of the TGF-&bgr; family is coexpressed with a mature region of another member of the TGF-&bgr; family, intracellular dimerization and secretion of biologically active homodimers occur (Gray, A., and Matson, A.,
Science,
247:1328, 1990). Additional studies by Hammonds, et al., (
Molec. Endocrin.
5:149, 1991) showed that the use of the BMP-2 pro-region combined with the BMP-4 mature region led to dramatically improved expression of mature BMP-4. For most of the family members that have been studied, the homodimeric species has been found to be biologically active, but for other family members, like the 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.
SUMMARY OF THE INVENTION
The present invention provides a cell growth and differentiation factor, Lefty-2, a polynucleotide sequence which encodes the factor, and antibodies which are bind to the factor. This factor appears to relate to various cell proliferative disorders.
Thus, in one embodiment, the invention provides a method for detecting a cell proliferative disorder which is associated with Lefty-2. In another embodiment, the invention provides a method for treating a cell proliferative or immunologic disorder by suppressing or enhancing Lefty-2 activity.
In another embodiment, the invention provides a method for identifying Lefty-2 receptor polypeptide comprising incubating components comprising Lefty-2 polypeptide and a cell expressing a receptor or a soluble receptor under conditions sufficient to allow the Lefty-2 to bind to the receptor; measuring the binding of the Lefty-2polypeptide to the receptor; and isolating the receptor. Methods of isolating the receptors are described in more detail in the Examples section.


REFERENCES:
patent: 5194596 (1993-03-01), Tischer et al.
patent: 5350836 (1994-09-01), Kopchick et al.
Benjamin et al., 1998, Development 125:1591-1598.*
Vukicevic et al., 1996, PNAS USA 93:9021-9026.*
Massague, 1987, Cell 49:437-438.*
Pilbeam et al., 1993, Bone 14:717-720.*
Skolnick et al., 2000, Trends in Biotech. 18:34-39.*
Bork, 2000, Genome Research 10:398-400.*
Doerks et al., 1998, Trends in Genetics 14:248-250.*
Smith et al., 1997, Nature Biotechnology 15:1222-1223.*
Brenner, 1999, Trends in Genetics 15:132-133.*
Bork, 1998, Trends in Genetics 12:425-427.*
Wells, 1990, Biochemistry 29:8509-8517.*
Ngo et al., 1994, The Protein Folding Problem and Tertiary Structure Prediction, Merz et al., eds., Birkhauser, Boston, pp. 492-495.*
Beddington, Rosa, “Left, Right, Left . . . Turn,” Nature 381:116-117, 1996.
Kosaki, K., et al., “Characterization and Mutation Analysis of HumanLefty AandLefty B, Homologues of Murine Genes Implicated in Left-Right Axis Development,” Am. J. Hum. Genet. 64:712-721, 1999.
Kothapalli, Ravi et al., “Detection ofebaf, a Novel Human Gene of the Transforming Growth Factor &bgr; Superfamily,” J. Clin. Invest. 99:(10)2342-2350, 1997.
Meno, Chikara et al., “Left-Right Asymmetric Expression of the TGF&bgr;-Family Memberleftyin Mouse Embryos,” Nature 381:151-155, 1996.
Meno, Chikara et al., “Lefty-1Is Required for Left-Right Determination as a Regulator oflefty-2andnodal,” Cell 94:287-297, 1998.
Schlange, Thomas et al., “Chick CFC Controls Lefty1 Expression in the Embryonic Midline and Nodal Expression in the Lateral Plate,” Developmental Biology 234:376-389, 2001.
Yoshioka, Hidefumi et al., “Pitx2, a Bicoid-Type Homeobox Gene, Is Involved in a Lefty-Signaling Pathway in Determination of Left-Right Asymmetry,” Cell 94:299-305, 1998.

Affiliated with

Also associated with

Rating

Growth differentiation factor, lefty-2 does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Growth differentiation factor, lefty-2, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Growth differentiation factor, lefty-2 will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3131848