Splicing variant of human membrane-type matrix metalloproteinase-5 (MT-MMP5-L)

Abstract

The MT-MMP5-L polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing MT-MMP5-L polypeptides and polynucleotides in therapy, and diagnostic assays for such.

What is claimed is:  
     
         1 . An isolated polypeptide selected from the group consisting of: 
 (i) an isolated polypeptide comprising an amino acid sequence selected from the group having at least: 
 (a) 70% identity;  
 (b) 80% identity;  
 (c) 90% identity; or  
 (d) 95% identity;  
 to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2;  
   (ii) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2; or    (iii) an isolated polypeptide which is the amino acid sequence of SEQ ID NO:2.    
     
     
         2 . An isolated polynucleotide selected from the group consisting of: 
 (i) an isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide that has at least 
 (a) 70% identity;  
 (b) 80% identity;  
 (c) 90% identity; or  
 (d) 95% identity;  
   to the amino acid sequence of SEQ ID NO:2, over the entire length of SEQ ID NO:2;    (ii) an isolated polynucleotide comprising a nucleotide sequence that has at least: 
 (a) 70% identity  
 (b) 80% identity;  
 (c) 90% identity; or  
 (d) 95% identity;  
   over its entire length to a nucleotide sequence encoding the polypeptide of SEQ ID NO:2;    (iii) an isolated polynucleotide comprising a nucleotide sequence which has at least: 
 (a) 70% identity;  
 (b) 80% identity;  
 (c) 90% identity; or  
 (d) 95% identity;  
   to that of SEQ ID NO: 1 over the entire length of SEQ ID NO: 1;    (iv) an isolated polynucleotide comprising a nucleotide sequence encoding the polypeptide of SEQ ID NO: 2;    (v) an isolated polynucleotide which is the polynucleotide of SEQ ID NO: 1; or    (vi) an isolated polynucleotide obtainable by screening an appropriate library under stringent hybridization conditions with a labeled probe having the sequence of SEQ ID NO: 1 or a fragment thereof.;    or a nucleotide sequence complementary to said isolated polynucleotide.    
     
     
         3 . An antibody immunospecific for the polypeptide of  claim 1 .  
     
     
         4 . A method for the treatment of a subject: 
 (i) in need of enhanced activity or expression of the polypeptide of  claim 1  comprising: 
 (a) administering to the subject a therapeutically effective amount of an agonist to said polypeptide; and/or  
 (b) providing to the subject an isolated polynucleotide comprising a nucleotide sequence encoding said polypeptide in a form so as to effect production of said polypeptide activity in vivo.; or  
   (ii) having need to inhibit activity or expression of the polypeptide of  claim 1  comprising: 
 (a) administering to the subject a therapeutically effective amount of an antagonist to said polypeptide; and/or  
 (b) administering to the subject a nucleic acid molecule that inhibits the expression of a nucleotide sequence encoding said polypeptide; and/or  
 (c) administering to the subject a therapeutically effective amount of a polypeptide that competes with said polypeptide for its ligand, substrate , or receptor.  
   
     
     
         5 . A process for diagnosing a disease or a susceptibility to a disease in a subject related to expression or activity of the polypeptide of  claim 1  in a subject comprising: 
 (a) determining the presence or absence of a mutation in the nucleotide sequence encoding said polypeptide in the genome of said subject; and/or  
 (b) analyzing for the presence or amount of said polypeptide expression in a sample derived from said subject.  
 
     
     
         6 . A method for screening to identify compounds which stimulate or which inhibit the function of the polypeptide of  claim 1  which comprises a method selected from the group consisting of: 
 (a) measuring the binding of a candidate compound to the polypeptide (or to the cells or membranes bearing the polypeptide) or a fusion protein thereof by means of a label directly or indirectly associated with the candidate compound;  
 (b) measuring the binding of a candidate compound to the polypeptide (or to the cells or membranes bearing the polypeptide) or a fusion protein thereof in the presence of a labeled competitor;  
 (c) testing whether the candidate compound results in a signal generated by activation or inhibition of the polypeptide, using detection systems appropriate to the cells or cell membranes bearing the polypeptide;  
 (d) mixing a candidate compound with a solution containing a polypeptide of  claim 1 , to form a mixture, measuring activity of the polypeptide in the mixture, and comparing the activity of the mixture to a standard; or  
 (e) detecting the effect of a candidate compound on the production of mRNA encoding said polypeptide and said polypeptide in cells, using for instance, an ELISA assay.  
 
     
     
         7 . An agonist or an antagonist of the polypeptide of  claim 1 .  
     
     
         8 . An expression system comprising a polynucleotide capable of producing a polypeptide of  claim 1  when said expression system is present in a compatible host cell.  
     
     
         9 . A process for producing a recombinant host cell comprising transforming or transfecting a cell with the expression system of  claim 8  such that the host cell, under appropriate culture conditions, produces a polypeptide comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2.  
     
     
         10 . A recombinant host cell produced by the process of  claim 9 .  
     
     
         11 . A membrane of a recombinant host cell of  claim 10  expressing a polypeptide comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2.  
     
     
         12 . A process for producing a polypeptide comprising culturing a host cell of  claim 10  under conditions sufficient for the production of said polypeptide and recovering the polypeptide from the culture.