Human aminoacyl-tRNA synthetase polypeptides useful for the regulation of angiogenesis
Compositions comprising truncated tryptophanyl-tRNA synthetase polypeptides useful for regulating angiogenesis, as well as nucleic acids encoding such tRNA synthetase polypeptides are described. Methods of making and using such compositions are also disclosed.
1. A method of suppressing angiogenesis in a mammal comprising the step of administering to the mammal an angiostatically effective amount of an isolated angiostatic truncated human tryptophanyl-tRNA synthetase (TrpRS) polypeptide comprising a carboxyl-terminal portion of human TrpRS that includes a Rossmann fold binding domain, wherein human TrpRS has the amino acid sequence of residues 1-471 of SEQ ID NO: 10, and the polypeptide does not comprise residues 1-47 of SEQ ID NO: 10.
2. The method of claim 1 , wherein the mammal is a human.
3. The method of claim 1 wherein the polypeptide comprises residues 71-471 of SEQ ID NO: 10.
4. The method of claim 1 wherein the polypeptide comprises residues 48-471 of SEQ ID NO: 10.
5. The method of claim 1 wherein the polypeptide has a molecular weight of about 47 kD and is produced by cleavage of human TrpRS with polymorphonuclear leucocyte elastase.
6. A method of treating, in a mammal, a condition that would benefit from decreased angiogenesis comprising the step of administering to the mammal an angiostatically effective amount of an isolated angiostatic truncated human tryptophanyl-tRNA synthetase (TrpRS) polypeptide or an isolated nucleic acid comprising a polynucleotide sequence encoding the polypeptide; the polypeptide comprising a carboxyl-terminal portion of human TrpRS and including a Rossmann fold binding domain, wherein human TrpRS has the amino acid sequence of residues 1-471 of SEQ ID NO: 10, and the polypeptide does not comprise residues 1-47 of SEQ ID NO: 10.
7. The method of claim 6 wherein the mammal is a human.
8. The method of claim 6 wherein the polypeptide comprises residues 71-471 of SEQ ID NO: 10.
9. The method of claim 6 wherein the polypeptide comprises residues 48-471 of SEQ ID NO: 10.
10. The method of claim 6 wherein the polypeptide has a molecular weight of about 47 kD and is produced by cleavage of human TrpRS with polymorphonuclear leucocyte elastase.
11. The method of claim 6 wherein the nucleic acid comprises a leader polynucleotide sequence fused to the polynucleotide sequence encoding the amino-terminal truncated human tryptophanyl-tRNA synthetase polypeptide and in an open reading frame therewith, the leader polynucleotide sequence encoding a secretory peptide sequence for controlling transport of the polypeptide from a cell.
12. The method of claim 6 wherein the condition comprises a solid tumor.
13. The method of claim 12 wherein the mammal is a human.
14. The method of claim 12 wherein the polypeptide comprises residues 71-471 of SEQ ID NO: 10.
15. The method of claim 12 wherein the polypeptide comprises residues 48-471 of SEQ ID NO: 10.
16. The method of claim 12 wherein the polypeptide has a molecular weight of about 47 kD and is produced by cleavage of human TrpRS with polymorphonuclear leucocyte elastase.
17. The method of claim 12 wherein the nucleic acid comprises a leader polynucleotide sequence fused to the polynucleotide sequence encoding the amino-terminal truncated human tryptophanyl-tRNA synthetase polypeptide and in an open reading frame therewith, the leader polynucleotide sequence encoding a secretory peptide sequence for controlling transport of the polypeptide from a cell.
18. The method of claim 6 wherein the condition comprises a tumor metastasis.
19. The method of claim 18 wherein the mammal is a human.
20. The method of claim 18 wherein the polypeptide comprises residues 71-471 of SEQ ID NO: 10.
21. The method of claim 18 wherein the polypeptide comprises residues 48-471 of SEQ ID NO: 10.
22. The method of claim 18 wherein the polypeptide has a molecular weight of about 47 kD and is produced by cleavage of human TrpRS with polymorphonuclear leucocyte elastase.
23. The method of claim 18 wherein the nucleic acid comprises a leader polynucleotide sequence fused to the polynucleotide sequence encoding the amino-terminal truncated human tryptophanyl-tRNA synthetase polypeptide and in an open reading frame therewith, the leader polynucleotide sequence encoding a secretory peptide sequence for controlling transport of the polypeptide from a cell.