Signal transduction inhibitors of allergic reactions

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence

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530328, C07K 706, C07K 1447

Patent

active

060840633

ABSTRACT:
The present invention provides an isolated polypeptide consisting of amino acids 1-66 of the human tyrosine kinase, Lyn A, in a pharmaceutically acceptable carrier and an isolated polypeptide consisting of amino acids 1-45 of the human tyrosine kinase, Lyn B, in a pharmaceutically acceptable carrier. The present invention also provides isolated nucleic acids encoding the above-described amino acid sequences, as well as vectors comprising the nucleic acids and cells comprising the vectors. The present invention further provides a method of treating or preventing an allergic disorder in a subject, comprising administering any of the above nucleic acids to a cell of the subject under conditions whereby the nucleic acid is expressed in the subject's cells, thereby treating the allergic disorder. Additionally provided in this invention is a fusion protein comprising either a polypeptide consisting of amino acids 1-66 of the human tyrosine kinase, Lyn A or a polypeptide consisting of amino acids 1-45 of the human tyrosine kinase, Lyn B and a ligand which binds to and is internalized by cells which express a high affinity receptor for IgE on the surface. A method of treating or preventing an allergic disorder in a subject is also provided, comprising administering an effective amount of the above fusion protein to a cell of the subject, whereby the fusion protein treats the subject's allergic disorder.

REFERENCES:
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Ucken et al. (1996) Physical and functional interactions between Lyn and p34cdc2 kinases in irradiated human B-cell precursors. J. Biol. Chem. 271:6389-6397, Mar. 1996.
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Pleiman et al. "Distinct p53/56.sup.lyn and p59.sup.fyn Domains Associate with Nonphosphorylated and Phosphorylated Ig-.alpha.", Proc. Natl. Acad. Sci. USA, 91:4268-4272, May 1994.
Rider et al. "The cDNAs Encoding Two Forms of the LYN Protein Tyrosine Kinase are Expressed in Rat Mast Cells and Human Myeloid Cells", Gene 138:219-222, 1994.
Resh, Marilyn D. "Interaction of Tyrosine Kinase Oncoproteins with Cellular Membranes", Biochimica et Biophysica Acta 1155:307-322, 1993.
Bolen et al. "The Src family of Tyrosine Protein Kinases in Hemopoietic Signal Transduction", FASEB J. 6:3403-3409, 1992.
Gauen et al. "p59.sup.fyn Tyrosine Kinase Associates with Multiple T-Cell Receptor Subunits Through its Unique Amino-Terminal Domain", 12(12):5438-5446, Dec. 1992, Mol. Cell. Biol.
Yamanashi et al. "The Yes-Related Cellular Gene Lyn Encodes a Possible Tyrosine Kinase Similar to p56.sup.lck ", Mol. and Cellular Biol., 7(1):237-243, Jan. 1987.

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