Nucleic acid encoding a G-protein-coupled receptor, and uses thereof

• US 20030186873A1
• Filed: 01/21/2003
• Published: 10/02/2003
• Est. Priority Date: 01/23/2002
• Status: Abandoned Application

• Current Assignee: Aventis Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
• Original Assignee: Aventis Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
• Inventors: Sandrasagra, Anthony, Cai, Jidong, Eishingdrelo, Haifeng
• Application Number:
  US10/348,083
• Publication Number:
  US 20030186873A1
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748

Abstract

Provided herein is a novel and useful G-protein coupled receptor that is involved in signal transduction with respect to inflammation and physiological immunological response. Also provided are methods of using the receptor to screen for molecules that may modulate the activity of the receptor. Such molecules may readily have applications in treating a plethora of inflammation and immunologically related diseases and disorders.

Claims

1. An isolated nucleic acid molecule comprising the DNA sequence of FIG. 1 (SEQ ID NO:

1).

2. An isolated nucleic acid molecule hybridizable to said isolated nucleic acid molecule of claim 1, or a hybridization probe that is complementary to said isolated nucleic acid molecule of claim 1, under stringent hybridization conditions.

3. The isolated nucleic acid molecule of either of claims 1 or 2 which encodes a polypeptide having an amino acid sequence of FIG. 2 (SEQ ID NO:

2).

4. The isolated nucleic acid molecule of claim 2, which encodes a polypeptide having an amino acid sequence that is at least 30% identical to said amino acid sequence of SEQ ID NO:

2.

5. The isolated nucleic acid molecule of either of claims 1 or 2, which is detectably labeled.

6. The detectably labeled isolated nucleic acid molecule of claim 5, wherein said detectable label comprises an enzyme, a radioactive isotope, or a chemical which fluoresces.

15. An expression vector comprising said isolated nucleic acid molecule of claim 1 operatively associated with an expression control element.

16. An expression vector comprising said isolated nucleic acid molecule of claim 2, operatively associated with an expression control element.

17. The expression vector of either of claims 15 or 16, wherein said expression control element is selected from the group consisting of a constitutive regulatory sequence, a cell-specific regulatory sequence, and an inducible regulatory sequence.

18. The expression vector of claim 17, wherein said expression control element is a promoter.

19. The expression vector of claim 18, wherein said promoter comprises an immediate early promoter of hCMV, an early promoter of SV40, an early promoter of adenovirus, an early promoter of vaccinia, an early promoter of polyoma, a late promoter of SV40, a late promoter of adenovirus, a late promoter of vaccinia, a late promoter of polyoma, a lac system, a trp system, a TAC system, a TRC system, a major operator and promoter region of phage lambda, a control region of fd coat protein, 3-phosphoglycerate kinase promoter, acid phosphatase promoter, or a promoter of yeast α

mating factor.

20. A host cell transformed or transfected with the expression vector of either of claims 15 or 16.

21. The host cell of claim 20, wherein said host cell comprises a prokaryotic cell or eukaryotic cell.

22. The host cell of claim 21, wherein said host comprises E. coli, Pseudonomas, Bacillus, Strepomyces, yeast, CHO, R1.1, B-W, L-M, COS1, COS7, BSC1, BSC40, BMT10 or Sf9 cells.

23. A method for producing the isolated polypeptide of claim 7, comprising the steps of:

a) culturing a host cell of claim 20 under conditions that provide for expression of said isolated polypeptide; and

b) recovering said isolated polypeptide from said host, said culture, or a combination thereof.

7. A purified polypeptide comprising the amino acid sequence of FIG. 2 (SEQ ID NO:

2).

8. An isolated nucleic acid molecule which encodes said purified polypeptide of claim 7.

9. The purified polypeptide of claim 7 which is detectably labeled.

10. The purified polypeptide of claim 9, wherein said detectable label comprises an enzyme, a radio active isotope, or a chemical which fluoresces.

11. An antibody having said purified polypeptide of claim 7 as an immunogen.

12. The antibody of claim 11, wherein said antibody is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, or a chimeric antibody.

13. The antibody of claim 11, which is detectably labeled.

14. The antibody of claim 13, wherein said detectable label comprises an enzyme, a radioactive isotope, or a chemical which fluoresces.

24. A therapeutic method for modulating GAVE6 signaling activity or signal transduction in a patient in need of treatment comprising administering to said patient an agonist, an antagonist or an inverse agonist of GAVE6.

25. A method for identifying an agonist of GAVE6 comprising:

contacting a potential agonist with a cell expressing GAVE6 and determining whether in the presence of said potential agonist the signaling activity of GAVE6 is increased relative to the activity of GAVE6 in the absence of said potential agonist.

26. A method for identifying an inverse agonist of GAVE6 comprising:

contacting a potential inverse agonist with a cell expressing GAVE6 and determining whether in the presence of said potential inverse agonist, the activity of GAVE6 is decreased relative to the activity of GAVE6 in the absence of said potential inverse agonist, and is decreased in the presence of an endogenous ligand or agonist.

27. A method for identifying an antagonist of GAVE6 comprising:

contacting a potential antagonist with a cell expressing GAVE6 and determining whether in the presence of said potential antagonist the signaling activity of GAVE6 is decreased relative to the activity of GAVE6 in the presence of an endogenous ligand or agonist.

28. A therapeutic composition comprising an agonist, an antagonist, or an inverse agonist of GAVE6 capable of modulating GAVE6 signaling activity or transduction.

29. A method for treating a disease comprising administering to a patient in need of treatment a therapeutic composition comprising an agonist, an antagonist or an inverse agonist of GAVE6 capable of modulating GAVE6 signaling activity or transduction.