Selectin ligands

Abstract

Podocalyxin like proteins (e.g. PCLP and PCLP-2) having selectin ligand activity are provided. Also provided are nucleic acid compositions encoding novel PCLP-2 proteins. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies for disease conditions associated with podocalyxin like protein activity. In particular, methods of treating diseases associated with podocalyxin like protein selectin binding activity and/or chemokine presenting activity are provided, where such diseases include inflammation and the like.

1 . Podocalyxin-like protein having selectin binding activity.  
     
     
         2 . The podocalyxin-like protein according to  claim 1 , wherein said protein is a glycoprotein.  
     
     
         3 . The podocalyxin-like protein according to  claim 2 , wherein said protein is derived from high endothelial venules.  
     
     
         4 . The podocalyxin-like protein according to  claim 3 , wherein said protein is derived from tonsilar high endothelial venules.  
     
     
         5 . A selectin ligand having the binding activity of the podocalyxin-like protein derived from high endothelial venules.  
     
     
         6 . The ligand according to  claim 5 , wherein said ligand is a ligand for L-selectin.  
     
     
         7 . The ligand according to  claim 5 , wherein said ligand is a ligand for P-selectin.  
     
     
         8 . The ligand according to  claim 5 , wherein said ligand is a glycoprotein.  
     
     
         9 . The ligand according to  claim 5 , wherein said ligand comprises an amino acid sequence found in human podocalyxin-like protein.  
     
     
         10 . The ligand according to  claim 5 , wherein said amino acid sequence is found in the membrane distal region of the protein.  
     
     
         11 . A pharmaceutical composition comprising an active agent that modulates the selectin binding activity of podocalyxin-like protein.  
     
     
         12 . The pharmaceutical composition according to  claim 11 , wherein said active agent is an agent that inhibits an enzyme responsible for post-translational modification of said protein, where said post-translational modification results in the selectin binding activity of said protein.  
     
     
         13 . The pharmaceutical composition according to  claim 11 , wherein said active agent modulates the expression of said podocalyxin-like protein.  
     
     
         14 . The pharmaceutical composition according to  claim 11 , wherein said active agent is a selectin ligand having the binding activity of the podocalyxin-like protein derived from high endothelial venules.  
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein said selectin ligand is a P-selectin ligand.  
     
     
         16 . The pharmaceutical composition according to  claim 14 , wherein said selectin ligand is an L-selectin ligand.  
     
     
         17 . A method for inhibiting a binding event between a selectin and podocalyxin-like protein, said method comprising: 
 contacting said selectin with a selectin ligand having the binding activity of podocalyxin-like protein.    
     
     
         18 . The method according to  claim 17 , wherein said selectin is P-selectin.  
     
     
         19 . The method according to  claim 17 , wherein said selectin is L-selectin.  
     
     
         20 . The method according to  claim 17 , wherein said binding event is an in vitro binding event.  
     
     
         21 . The method according to  claim 17 , wherein said binding event is an in vivo binding event.  
     
     
         22 . A method of inhibiting a selectin mediated binding event in a mammalian host, said method comprising: 
 administering to said host an effective amount of a pharmaceutical composition comprising an active agent that modulates the selectin binding activity of podocalyxin-like protein.    
     
     
         23 . The method according to  claim 22 , wherein said active agent inhibits an enzyme responsible for post-translational modification of said protein, where said post-translational modification results in the selectin binding activity of said protein.  
     
     
         24 . The method according to  claim 22 , wherein said active agent modulates the expression of said podocalyxin-like protein.  
     
     
         25 . The method according to  claim 22 , wherein said active agent is a selectin ligand having the binding activity of the podocalyxin-like protein derived from high endothelial venules.  
     
     
         26 . The method according to according to  claim 25 , wherein said selectin ligand is a P-selectin ligand.  
     
     
         27 . The method according to  claim 25 , wherein said selectin ligand is an L-selectin ligand.  
     
     
         28 . A method of modulating a symptom in a mammalian host of a disease condition associated with a selectin mediated binding, said method comprising: 
 administering to said host a pharmaceutical composition comprising an effective amount of an active agent that modulates the selectin binding activity of high endothelial venule podocalyxin-like protein.    
     
     
         29 . The method according to  claim 28 , wherein said symptom is inflammation.  
     
     
         30 . The method according to  claim 28 , wherein said disease condition is selected from the group consisting of acute inflammation, chronic inflammation, autoimmune disease, tissue rejection, atherosclerosis, restinosis, and damaging thombotic event.