Novel tyrosine kinase receptors and ligands
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsDavid M. Valenzuela, David J. Glass, David C. Bowen, George D. Yancopoulos
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Abstract
The present invention provides for a gene, designated as musk, that encodes a novel tyrosine kinase receptor expressed in high levels in denervated muscle. The invention also provides for an isolated polypeptide which activates MuSK receptor. The invention further provides for a polypeptide which is functionally equivalent to the MuSK activating polypeptide. The invention also provides assay systems that may be used to detect and/or measure ligands that bind the musk gene product. The present invention also provides for diagnostic and therapeutic methods based on molecules that activate MuSK.
Claims63
An isolated nucleic acid molecule comprising a nucleotide sequence encoding the active portion of human agrin, wherein the nucleotide sequence is selected from the group consisting of:
- (a) the nucleotide sequence comprising the coding region of the active portion of human agrin contained in the vector designated as pBL-hAgrin 1 (ATCC Accession No. 97378);
- (b) a nucleotide sequence that hybridizes under stringent conditions to the nucleotide sequence of (a) and which encodes the active portion of human agrin;
- and
- (c) a nucleotide sequence that, as a result of the degeneracy of the genetic code, differs from the nucleotide sequence of (a) or (b) and which encodes the active portion of human agrin.
An isolated nucleic acid molecule comprising a nucleotide sequence encoding the active portion of human agrin, wherein the nucleotide sequence is selected from the group consisting of:
- (a) the nucleotide sequence as set forth in FIG. 15;
- (b) the nucleotide sequence encoding amino acids 24 to 492 as set forth in FIG. 15;
- (c) the nucleotide sequence encoding amino acids 60 to 492 as set forth in FIG. 15;
- (d) the nucleotide sequence encoding amino acids 76 to 492 as set forth in FIG. 15;
- (e) the nucleotide sequence encoding amino acids 126 to 492 as set forth in FIG. 15;
- (f) the nucleotide sequence encoding amino acids 178 to 492 as set forth in FIG. 15;
- (g) the nucleotide sequence encoding amino acids 222 to 492 as set forth in FIG. 15;
- (h) the nucleotide sequence encoding amino acids 260 to 492 as set forth in FIG. 15;
- (i) the nucleotide sequence encoding amino acids 300 to 492 as set forth in FIG. 15;
- (j) a nucleotide sequence that hybridizes under stringent conditions to any of the nucleotide sequences of (a) through (i) and which encodes the active portion of human agrin;
- and
- (k) a nucleotide sequence that, as a result of the degeneracy of the genetic code, differs from any of the nucleotide sequences of (a) through (j) and which encodes the active portion of human agrin.
A method of promoting the growth, differentiation or survival of a MuSK receptor expressing cell comprising administering to the cell an effective amount of agrin.
Dependencies are inferred from the claim text.