Thrombopoietic activity of tyrosyl-trna synthetase polypeptides

Abstract

Thrombopoietic compositions are provided comprising tyrosyl tRNA synthetase polypeptides, including truncations and/or variants thereof. Also provided are methods of using such compositions in the treatment of conditions that benefit from increased thrombopoiesis, such as thrombocytopenia.

1 - 26 . (canceled) 
     
     
         27 . A composition adapted for administration, comprising a physiologically acceptable excipient and/or carrier and a tyrosyl-tRNA synthetase polypeptide having a cell-signaling activity. 
     
     
         28 - 40 . (canceled) 
     
     
         41 . The composition of  claim 27 , wherein the tyrosyl-tRNA synthetase polypeptide is selected from:
 (a) a polypeptide comprising an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO: 1, 2, 3, 6, 8, 10, 12, or 14;   (b) a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 1, 2, 3, 6, 8, 10, 12, or 14;   (c) a polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 1, 2, 3, 6, 8, 10, 12, or 14;   (d) a polypeptide comprising an amino acid sequence at least 98% identical to the amino acid sequence set forth in SEQ ID NO: 1, 2, 3, 6, 8, 10, 12, or 14; and   (e) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1, 2, 3, 6, 8, 10, 12, or 14.   
     
     
         42 . The composition of  claim 27 , further comprising a second tyrosyl-tRNA synthetase polypeptide, wherein the two tyrosyl-tRNA synthetase polypeptides form a dimer. 
     
     
         43 . The composition of  claim 42 , wherein the dimer is a homodimer. 
     
     
         44 . The composition of  claim 43 , wherein the dimer is a heterodimer. 
     
     
         45 . The composition of  claim 44 , wherein the heterodimer comprises a full-length tyrosyl-tRNA synthetase polypeptide and a truncated tyrosyl-tRNA synthetase polypeptide. 
     
     
         46 . The composition of  claim 27 , further comprising a heterologous polypeptide, wherein the tyrosyl-tRNA synthetase polypeptide and the heterologous polypeptide form a heterodimer. 
     
     
         47 - 65 . (canceled) 
     
     
         66 . The composition of  claim 27 , wherein the tyrosyl-tRNA synthetase polypeptide is selected from:
 (a) a polypeptide comprising an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO: 8;   (b) a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 8;   (c) a polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 8;   (d) a polypeptide comprising an amino acid sequence at least 98% identical to the amino acid sequence set forth in SEQ ID NO: 8; and   (e) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 10.   
     
     
         67 . The composition of  claim 66 , where the tyrosyl-tRNA synthetase polypeptide is up to about 400 amino acids in length.