Nucleic acid encoding cytokine receptor zcytor17

• US 20050214801A1
• Filed: 11/05/2004
• Published: 09/29/2005
• Est. Priority Date: 06/26/2000
• Status: Abandoned Application

• Current Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Inventors: Gao, Zeren, Presnell, Scott R., Sprecher, Cindy A., Whitmore, Theodore E., Maurer, Mark F., Kuijper, Joseph L.
• Application Number:
  US10/982,555
• Publication Number:
  US 20050214801A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons

Abstract

Novel polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for zcytor17, a novel cytokine receptor. The polypeptides may be used within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block ligand activity in vitro and in vivo. The polynucleotides encoding zcytor17, are located on chromosome 5, and can be used to identify a region of the genome associated with human disease states. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

Claims

1. An isolated polynucleotide encoding a polypeptide, wherein the encoded polypeptide comprises a sequence of amino acid residues that is selected from the group consisting of:

(a) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to amino acid number 227 (Pro);

(b) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to amino acid number 519 (Glu);

(c) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to amino acid number 543 (Leu);

(d) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 544 (Lys) to amino acid number 732 (Val);

(e) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to amino acid number 732 (Val); and

(f) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 1 (Met) to amino acid number 732 (Val).

3. An isolated polynucleotide according to claim 1, wherein the encoded polypeptide has activity as measured by cell proliferation, activation of transcription of a reporter gene, or wherein the encoded polypeptide further binds to an antibody,

wherein the antibody is raised to a polypeptide comprising a sequence of amino acids selected from the group consisting of:

(a) the polypeptide comprising amino acid number 20 (Ala) to 227 (Pro) of SEQ ID NO;

2;

(b) the polypeptide comprising amino acid number 20 (Ala) to 519 (Glu) of SEQ ID NO;

2;

(c) the polypeptide comprising amino acid number 20 (Ala) to 543 (Leu) of SEQ ID NO;

2;

(d) the polypeptide comprising amino acid number 544 (Lys) to 732 (Val) of SEQ ID NO;

2;

(e) the polypeptide comprising amino acid number 20 (Ala) to 732 (Val) of SEQ ID NO;

2; and

(f) the polypeptide comprising amino acid number 1 (Met) to 732 (Val) of SEQ ID NO;

2; and

wherein the binding of the antibody to the isolated polypeptide is measured by a biological or biochemical assay including radioimmunoassay, radioimmuno-precipitation, Western blot, or enzyme-linked immunosorbent assay.

2. An isolated polynucleotide comprising a sequence selected from the group consisting of:

(a) a polynucleotide as shown in SEQ ID NO;

1 from nucleotide number 228 to amino acid number 851;

(b) a polynucleotide as shown in SEQ ID NO;

1 from nucleotide number 228 to amino acid number 1727;

(c) a polynucleotide as shown in SEQ ID NO;

1 from nucleotide number 228 to amino acid number 1799;

(d) a polynucleotide as shown in SEQ ID NO;

1 from nucleotide number 1800 to amino acid number 2366;

(e) a polynucleotide as shown in SEQ ID NO;

1 from nucleotide number 228 to amino acid number 2366;

(f) a polynucleotide as shown in SEQ ID NO;

1 from nucleotide number 171 to amino acid number 2366; and

(g) a polynucleotide sequence complementary to (a) through (f).

4. An expression vector comprising the following operably linked elements:

a transcription promoter;

a DNA segment encoding a polypeptide comprising an amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to 732 (Val); and

a transcription terminator,

wherein the promoter is operably linked to the DNA segment, and the DNA segment is operably linked to the transcription terminator.

5. An expression vector according to claim 4, further comprising a secretory signal sequence operably linked to the DNA segment.

6. A cultured cell comprising an expression vector according to claim 4, wherein the cell expresses a polypeptide encoded by the DNA segment.

7. An expression vector comprising the following operably linked elements:

a transcription promoter;

a DNA segment encoding a polypeptide comprising an amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to 227 (Pro);

or as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to 519 (Glu); and

a transcription terminator,

wherein the promoter, DNA segment, and terminator are operably linked.

8. An expression vector according to claim 7, further comprising a secretory signal sequence operably linked to the DNA segment.

9. An expression vector according to claim 7, wherein the polypeptide further comprises a transmembrane domain consisting of residues 520 (Ile) to 543 (Leu) of SEQ ID NO:

2.

10. An expression vector according to claim 7 wherein the polypeptide further comprises an intracellular domain consisting of residues 544 (Lys) to 732 (Val) of SEQ ID NO:

2.

11. A cultured cell into which has been introduced an expression vector according to claim 7, wherein the cell expresses a soluble receptor polypeptide encoded by the DNA segment.

16. A method of producing a polypeptide comprising:

culturing a cell according to claim 11;

and

isolating the polypeptide produced by the cell.

12. A DNA construct encoding a fusion protein, the DNA construct comprising:

a first DNA segment encoding a polypeptide comprising a sequence of amino acid residues selected from the group consisting of;

(a) the amino acid sequence of SEQ ID NO;

2 from amino acid number 1 (Met), to amino acid number 19 (Ala);

(b) the amino acid sequence of SEQ ID NO;

2 from amino acid number 20 (Ala), to amino acid number 227 (Pro);

(c) the amino acid sequence of SEQ ID NO;

2 from amino acid number 20 (Ala), to amino acid number 519 (Glu);

(d) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to amino acid number 543 (Leu);

(e) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 520 (Ile) to amino acid number 543 (Leu);

(f) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 544 (Lys) to amino acid number 732 (Val); and

(g) the amino acid sequence as shown in SEQ ID NO;

2 from amino acid number 20 (Ala) to amino acid number 732 (Val); and

at least one other DNA segment encoding an additional polypeptide,

wherein the first and other DNA segments are connected in-frame; and

wherein the first and other DNA segments encode the fusion protein.

13. An expression vector comprising the following operably linked elements:

a transcription promoter;

a DNA construct encoding a fusion protein according to claim 12;

and

a transcription terminator,

wherein the promoter is operably linked to the DNA construct, and the DNA construct is operably linked to the transcription terminator.

14. A cultured cell comprising an expression vector according to claim 13, wherein the cell expresses the fusion protein encoded by the DNA construct.

15. A method of producing a fusion protein comprising:

culturing a cell according to claim 14;

and

isolating the fusion protein produced by the cell.

17. An isolated soluble receptor polypeptide comprising amino acid residues 20-519 of SEQ ID NO:

2.

18. The isolated soluble receptor polypeptide of claim 17 wherein the isolated soluble receptor polypeptide is fused to an immunoglobulin heavy chain constant region.

19. The isolated soluble receptor polypeptide of claim 18 wherein the immunoglobulin heavy chain constant region is a human immunoglobulin F_c4 fragment.

20. An isolated polypeptide comprising amino acid residues 20-732 of SEQ ID NO:

2.

21. An isolated polynucleotide encoding a soluble receptor polypeptide wherein the soluble receptor polypeptide comprises amino acid residues 20-519 of SEQ ID NO:

2.

22. The isolated polynucleotide of claim 21 wherein the soluble receptor polypeptide is fused to an immunoglobulin heavy chain constant region.

23. The isolated polynucleotide of claim 22 wherein wherein the immunoglobulin heavy chain constant region is a human immunoglobulin F_c4 fragment.

24. An expression vector comprising the following operably linked elements:

a transcription promoter;

a DNA segment encoding a soluble receptor polypeptide comprising amino acid residues 20-519 of SEQ ID NO;

2; and

a transcription terminator,

wherein the promoter is operably linked to the DNA segment, and the DNA segment is operably linked to the transcription terminator.

25. The expression vector of claim 24 further comprising a secretory signal sequence operably linked to the DNA segment.

26. The expression vector of claim 24 further comprising an immunoglobulin heavy chain constant region operably linked to the DNA segment.

27. The expression vector of claim 26 wherein the immunoglobulin heavy chain constant region is a human immunoglobulin F_c4 fragment.

28. A cultured cell comprising an expression vector according to claim 24, wherein the cell expresses the soluble receptor polypeptide encoded by the DNA segment.