Claims
- 1. An isolated nucleic acid molecule which encodes a TLT-1 polypeptide, or a complement thereof, wherein the TLT-1 polypeptide can modulate platelet function.
- 2. The nucleic acid molecule of claim 1, wherein the TLT-1 polypeptide is membrane-bound, or a complement thereof.
- 3. The nucleic acid molecule of claim 1, wherein the TLT-1 polypeptide is a soluble TLT-1 extracellular domain, or a complement thereof.
- 4. The nucleic acid molecule of claim 1, which encodes a murine TLT-1 polypeptide, or a complement thereof.
- 5. The nucleic acid molecule of claim 1, which encodes a human TLT-1 polypeptide, or a complement thereof.
- 6. An isolated nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, 3, 4, 6, 18, 20, 21, 23, 24, or 26, or a complement thereof.
- 7. An isolated nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, 5, 19, 22, or 25, or a complement thereof.
- 8. An isolated nucleic acid molecule selected from the group consisting of:
(a) a nucleic acid molecule comprising a nucleotide sequence which is at least about 97% identical to the nucleotide sequence of SEQ ID NO:1 or 3, or a complement thereof; (b) a nucleic acid molecule comprising a nucleotide sequence which is at least about 60% identical to the nucleotide sequence of SEQ ID NO:1, 3, 4, 6, 18, 20, 21, 23, 24, or 26, or a complement thereof, or a complement thereof; (c) a nucleic acid molecule comprising at least 487 nucleotides of SEQ ID NO:1 or 3, or a complement thereof; (d) a nucleic acid molecule comprising at least 336 nucleotides of SEQ ID NO:4 or 6, or a complement thereof; (e) a nucleic acid molecule comprising at least 30 nucleotides of SEQ ID NO:1, 3, 4, 6, 18, 20, 21, 23, 24, and 26, or a complement thereof (f) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence which is at least about 99% identical to the amino acid sequence of SEQ ID NO:2, or a complement thereof; (g) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence which is at least about 81% identical to the amino acid sequence of SEQ ID NO:5, or a complement thereof; (h) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence which is at least about 60% identical to the amino acid sequence of SEQ ID NO:2, 5, 19, 22, or 25, or a complement thereof; (i) a nucleic acid molecule which encodes at least 173 contiguous amino acid residues of SEQ ID NO:2, or a complement thereof; (j) a nucleic acid molecule which encodes at least 111 contiguous amino acid residues of SEQ ID NO:5, or a complement thereof; and (k) a nucleic acid molecule which encodes at least 10 contiguous amino acid residues of SEQ ID NO:2, 5, 19, 22, or 25, or a complement thereof.
- 9. An isolated nucleic acid molecule which hybridizes to a complement of the nucleic acid molecule of any one of claims 1-8 under stringent conditions.
- 10. An isolated nucleic acid molecule comprising the nucleic acid molecule of any one of claims 1-8 and a nucleotide sequence encoding a heterologous polypeptide.
- 11. A vector comprising the nucleic acid molecule of any one of claims 1-8.
- 12. The vector of claim 11, which is an expression vector.
- 13. A host cell transfected with the expression vector of claim 12.
- 14. A method of producing a polypeptide comprising culturing the host cell of claim 13 in an appropriate culture medium to, thereby, produce the polypeptide.
- 15. An isolated TLT-1 polypeptide, wherein the TLT-1 polypeptide can modulate platelet function.
- 16. The polypeptide of claim 15, wherein the TLT-1 polypeptide is membrane-bound.
- 17. The polypeptide of claim 15, wherein the TLT-1 polypeptide is a soluble TLT-1 extracellular domain.
- 18. The polypeptide of claim 15, which encodes a murine TLT-1 polypeptide.
- 19. The polypeptide of claim 15, which encodes a human TLT-1 polypeptide.
- 20. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2, 5, 19, 22, or 25.
- 21. An isolated polypeptide selected from the group consisting of:
(a) a polypeptide comprising at least 173 contiguous amino acid residues of SEQ ID NO:2; (b) a polypeptide comprising at least 111 contiguous amino acid residues of SEQ ID NO:5; (c) a polypeptide comprising at least 10 contiguous amino acid residues of SEQ ID NO:2, 5, 19, 22, or 25. (d) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least about 97% identical to the nucleotide sequence of SEQ ID NO:1 or 3; (e) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least about 60% identical to the nucleotide sequence of SEQ ID NO:1, 3, 4, 6, 18, 20, 21, 23, 24, and 26; (f) a polypeptide comprising an amino acid sequence which is at least about 99% identical to the amino acid sequence of SEQ ID NO:2; (g) a polypeptide comprising an amino acid sequence which is at least about 81% identical to the amino acid sequence of SEQ ID NO:5; and (h) a polypeptide comprising an amino acid sequence which is at least about 60% identical to the amino acid sequence of SEQ ID NO:2, 5, 19, 22, or 25.
- 22. The polypeptide of any one of claims 15-21, further comprising heterologous amino acid sequences.
- 23. An antibody which selectively binds to a polypeptide of any one of claims 15-21.
- 24. A method for detecting the presence of a polypeptide of any one of claims 15-21 in a sample comprising:
a) contacting the sample with a compound which selectively binds to the polypeptide; and b) determining whether the compound binds to the polypeptide in the sample to thereby detect the presence of a polypeptide of any one of claims 15-21 in the sample.
- 25. The method of claim 24, wherein the compound which binds to the polypeptide is an antibody.
- 26. A kit comprising a compound which selectively binds to a polypeptide of any one of claims 15-21 and instructions for use.
- 27. A method for detecting the presence of a nucleic acid molecule of any one of claims 1-8 in a sample comprising:
a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample to thereby detect the presence of a nucleic acid molecule of any one of claims 1-8 in the sample.
- 28. The method of claim 27, wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.
- 29. A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of any one of claims 1-8 and instructions for use.
- 30. A method for identifying a compound which binds to a polypeptide of any one of claims 15-21 comprising:
a) contacting the polypeptide, or a cell expressing the polypeptide with a test compound; and b) determining whether the polypeptide binds to the test compound.
- 31. The method of claim 30, wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of:
a) detection of binding by direct detection of test compound/polypeptide binding; b) detection of binding using a competition binding assay; and c) detection of binding using an assay for TLT-1 activity.
- 32. A method for modulating the activity of a polypeptide of any one of claims 15-21 comprising contacting the polypeptide, or a cell expressing the polypeptide, with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.
- 33. A method for identifying a compound which modulates the activity of a polypeptide of any one of claims 15-21 comprising:
a) contacting a polypeptide of any one of claims 15-21 with a test compound; and b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.
- 34. A method for identifying a compound capable of treating a disorder selected from the group consisting of septic shock, cancer, infectious disease, stroke, heart disease, myocardial infarction, arteriosclerosis, clotting disorders, bleeding disorders, platelet insufficiency, and a TLT-1 associated disorder, comprising assaying the ability of the compound to modulate TLT-1 nucleic acid expression or TLT-1 polypeptide activity, thereby identifying a compound capable of treating a disorder selected from the group consisting of septic shock, cancer, infectious disease, stroke, heart disease, myocardial infarction, arteriosclerosis, clotting disorders, bleeding disorders, platelet insufficiency, and a TLT-1 associated disorder.
- 35. A method for treating a subject having a disorder selected from the group consisting of septic shock, cancer, infectious disease, stroke, heart disease, myocardial infarction, arteriosclerosis, clotting disorders, bleeding disorders, platelet insufficiency, and a TLT-1 associated disorder, comprising administering to the subject a therapeutically effective amount of a TLT-1 modulator, thereby treating said subject having a disorder selected from the group consisting of septic shock, cancer, infectious disease, stroke, heart disease, myocardial infarction, arteriosclerosis, clotting disorders, bleeding disorders, platelet insufficiency, and a TLT-1 associated disorder.
- 36. The method of claim 35, wherein the TLT-1 modulator is a TLT-1 polypeptide.
- 37. The method of claim 36, wherein the TLT-1 polypeptide is a soluble TLT-1 extracellular domain.
- 38. The method of claim 35, wherein the TLT-1 modulator is an antibody that selectively binds to TLT-1.
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application Serial No. 60/455,370, filed Mar. 16, 2003, the entire contents of which are incorporated herein by this reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60455370 |
Mar 2003 |
US |