Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1997-02-21
1999-06-15
Scheiner, Toni R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 12, 514291, 424 851, 4241981, 530399, A61K 3133, A61K 3818
Patent
active
059122242
ABSTRACT:
The present invention concerns the TGF-.beta. receptor-mediated signaling pathway. The invention is based on the unexpected finding that TGF-.beta. receptor-mediated signaling is inhibited by the cytoplasmic interactor FKBP12. The invention further concerns methods and pharmaceutical compositions for enhancing cellular response to TGF-.beta. ligands. A screening assay is also provided for identifying macrolide potentiators capable of binding FKBP12 and thereby blocking FKBP12-inhibition of TGF-.beta. receptor-mediated signaling.
REFERENCES:
patent: 4885171 (1989-12-01), Surendra
patent: 5008240 (1991-04-01), Bentz
patent: 5011687 (1991-04-01), Donahoe
patent: 5286730 (1994-02-01), Caufield
patent: 5310880 (1994-05-01), Donahoe
patent: 5387589 (1995-02-01), Kulkarni
patent: 5411940 (1995-05-01), Nixon
patent: 5436228 (1995-07-01), Postlethwaite et al.
Andres, D.A., et al., "Mutational Analysis of .alpha.-Subunit of Protein Farnesyltransferase. Evidence for a Catalytic Role," J. Biol. Chem. 268(2):1383-1390 (1993).
Andres, D.A., et al., "cDNA Cloning of the Two Subunits of Human CAAX Farnesyltransferase and Chromosomal Mapping of FNTA and FNTB Loci and Related Sequences," Genomics 18(1):105-112 (1993).
Bassing, C.H., et al., "A Transforming Growth Factor .beta. Type I Receptor That Signals to Activate Gene Expression," Science 263:87-89 (1994).
Becker, J.W., et al., "FK-506-binding Protein: Three-dimensional Structure of the Complex with the Antagonist L-685,818," J. Biol. Chem. 268(15):11335-11339 (1993).
Brown, E.J., et al., "Control of p70 S6 kinase activity of FRAP in vivo," Nature 377:441-446 (Oct. 1995).
Cameron, A.M., et al., "Immunophilin FK506 bindig protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux," Proc. Natl. Acad. Sci. USA 92:1784-1788 (Feb. 1995).
Cameron, A.M., et al., "Calcineurin Associated with the Inositol 1,4,5-Trisphosphate Receptor-FKBP12 Complex Modulates Ca.sup.2+ Flux," Cell 83:463-472 (Nov. 1995).
Cate, R.L., et al., "Isolation of the Bovine and Human Genes for Mellerian Inhibiting Substance and Expression of the Human Gene in Animal Cells," Cell 45:685-698 (1986).
Derynck, R., et al., "A new type of transforming growth factor-.beta., TGF-.beta.3," EMBO J. 7(12):3737-3743 (1988).
Donahoe, P.K., et al., "A Graded Organ Culture Assay for the Detection of Mullerian Inhibiting Substance," J. Surg. Res. 23:141-148 (1977).
Ebner, R., et al., "Cloning of a Type I TGF-.beta. Receptor and Its Effect on TGF-.beta. Binding to the Type II Receptor," Science 260:1344-1348 (1993).
Forage, R.G., et al., "Cloning and sequence analysis of cDNA species coding for the two subunits of inhibin from bovine follicular fluid," Proc. Natl. Acad. Sci. USA 83:3091-3095 (1986).
Franzen, P., et al., "Cloning of a TGF.beta. Type I Receptor That Forms a Heteromeric Complex with the TGF.beta. Type II Receptor," Cell 75:681-692 (1993).
Galat, A., et al., "A Rapamycin-Selective 25-kDa Immunophilin," Biochemistry 31:2427-2434 (1992).
Gyuris, J., et al., "Cdi1, a Human G1 and S Phase Protein Phosphatase That Associated with Cdk2," Cell 75:791-803 (1993).
He, W.W., et al., "Developmental Expression of Four Novel Serine/Threonine Kinase Receptors Homologous to the Activin/Transforming Growth Factor-.beta. Type II Receptor Family," Dev. Dyn. 196:133-142 (1993).
Laiho, M., et al., "Concomitant Loss of Transforming Growth Factor (TGF)-.beta. Receptor Types I and II in TGF-.beta.-resistant Cell Mutants Implicates Both Receptor Types in Signal Transduction," J. Biol. Chem. 265(30):18518-18524 (1990).
Lin, H.Y., et al., "Expression Cloning of the TGF-.beta. Type II Receptor, a Functional Transmembrane Serine/Threonine Kinase," Cell 68:775-785 (1992).
Liu, J., et al., "Inhibition of T Cell Signaling by Immunophilin-Ligand Complexes Correlates with Loss of Calcineurin Phosphatase Activity," Biochemistry 31:3896-3901 (1992).
Lyons, K., et al., "Vgr-1, a mammalian gene related to Xenopus Vg-1, is a member of the transforming growth factor .beta. gene superfamily," Proc. Natl. Acad. Sci. USA 86:4554-4558 (1989).
McAlpine, J.B., et al., "Revised NMR Assignments for Rapamycin," J. Antibiotics 44(6):688-690 (1991).
MacLaughlin, D.T., et al., "Mullerian Duct Regression and Antiproliferative Bioactivities of Mullerian Inhibiting Substance Reside in its Carboxy-Terminal Domain," Endocrinology 131(1):1-6 (1992).
Mulder, K.M., and Morris, S.L., "Activation of p21.sup.ras by Transforming Growth Factor .beta. in Epithelial Cells," J. Biol. Chem. 267(8):5029-5031 (1992).
Padgett, R.W., et al., "A transcript from a Drosphila pattern gene predicts a protein homologous to the transforming growth factor-.beta. family," Nature 325:81-84 (1987).
Rotonda, J., et al., "Improved Calcineurin Inhibition by Yeast FKBP12-Drug Complexes," J. Biol. Chem. 268(11):7607-7609 (1993).
Sabatini, D.M., et al., "RAFT1: A Mammalian Protein That Binds to FKBP12 in a Rapamycin-Dependent Fashion and Is Homologous to Yeast TORs," Cell 78:35-43 (1994).
Schreiber, S.L., "Chemistry and Biology of the Immunophilins and Their Immunosuppressive Ligands," Science 251:283-287 (1991).
Siekierka, J.J., et al., "A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin," Nature 341:755-757 (1989).
Standaert, R.F., et al., "Molecular cloning and overexpression of the human FK506-binding protein FKBP," Nature 346:671-674 (1990).
Tanaka, H., et al., "Structure of FK506: A Novel Immunosuppressant Isolated from Streptomyces," J. Am. Chem. Soc. 109:5031-5033 (1987).
Trelstad, R.L., et al., "The Epithelial-Mesenchymal Interface of the Male Rat Mullerian Duct: Loss of Basement Membrane Integrity and Ductal Regression," Devl. Biol. 92:27-40 (1982).
Wang, T., et al., "Specific Interaction of Type I Receptors of the TGF-.beta. Family with the Immunophilin FKBP-12," Science 265:674-676 (1994).
Wang, T., et al., "The Immunophilin FKBP12 Functions as a Common Inhibitor of the TGF.beta. Family Type I Receptors," Cell 86:435-444 (Aug. 1996).
Wang, T., et al., "The p21.sup.ras Farnesyltransferase .alpha. Subunit in TGF-.beta. and Activin Signaling," Science 271:1120-1122 (Feb. 23, 1996).
Wieser, R., et al., "GS domain mutations that constitutively activate T.beta.R-I, the downstream signaling component in the TGF-.beta. receptor complex," EMBO J. 14(10):2199-2208 (May 1995).
Wozney, J.M., et al., "Novel Regulators of Bone Formation: Molecular Clones and Activities," Science 242:1528-1534 (1988).
Wrana, J.L., et al., "TGF.beta. Signals through a Heteromeric Protein Kinase Receptor Complex," Cell 71(6):1003-1014 (1992).
Wrana, J.L., et al., "Mechanism of activation of the TGF-.beta. receptor," Nature 370:341-347 (1994).
Xie, T., et al., "The Drosphila saxophone Gene: A Serine-Threonine Kinase Receptor of the TGF-.beta. Superfamily," Science 263:1756-1759 (1994).
Brummel, T.J. et al., "Characterization and Relationship of Dpp Receptors encoded by the saxophone and thick veins Genes in Drosophila," Cell 78:251-261 (1994).
ten Dijke, P. et al., "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity," Oncogene 8:2879-2887 (1993).
ten Dijke, P. et al., "Characterization of Type I Receptors for Transforming Growth Factor-.beta. and Activin," Science 264:101-104 (1994).
Thomson, A.W. et al., "Mode of Action of Tacrolimus (FK506): Molecular and Cellular Mechanisms," Ther. Drug Monit. 17(6):584-591 (Dec. 1995).
Charng, M.J. et al., "FKBP-12 Recognition Is Dispensable For Signal Generation by Type I Transforming Growth Factor-.beta. Receptors," J. Biol. Chem. 271(38):22941-22944 (Sep. 1996).
Okadome, T. et al., "Characterization of the Interaction of FKBP12 with the Transforming Growth Factor-.beta. Type I Receptor in Vivo," J. Biol. Chem. 271(360):21687-21690 (Sep. 1996).
Rao, P. et al., "Effect of FK 506 on FK-Binding Protein and Transforming Growth Factor Beta Gene Expression," Trans. Proc. 23(6):2873-2874 (1991).
Palladino, Annals NY Acad. Sci. 593:181, 1990.
Donahoe Patricia K.
Wang Tongwen
Johnson Nancy A.
Scheiner Toni R.
The General Hospital Corporation
LandOfFree
Methods and compositions for enhancing cellular response to TGF- does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and compositions for enhancing cellular response to TGF-, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for enhancing cellular response to TGF- will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-402483