Hodge, Martin R.;

Kinases and uses thereof

Novel kinase polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length kinase proteins, the invention further provides isolated kinase fusion proteins, antigenic peptides, and anti-kinase antibodies. The invention also provides kinase nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a kinase gene has been introduced or disrupted. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

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What is claimed is:

1. An isolated nucleic acid molecule selected from the group consisting of:

a) a nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide having a kinase protein activity and which is at least 85% identical to the nucleotide sequence of SEQ ID NO:1, to nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof;

b) a nucleic acid molecule comprising a fragment of at least 325 nucleotides of the nucleotide sequence of SEQ ID NO:1 or a complement thereof, wherein said fragment encodes a polypeptide having a kinase protein activity;

c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2;

d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2; wherein the fragment has a kinase protein activity and comprises at least 75 contiguous amino acids of SEQ ID NO:2; and

e) a nucleic acid molecule which encodes a variant of the polypeptide comprising the amino acid sequence of SEQ ID NO:2, said variant having a kinase protein activity, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof under stringent conditions, said stringent conditions comprising hybridization in 6.times.SSC at 42.degree. C., followed by washing with 1.times.SSC at 55.degree. C.

2. The isolated nucleic acid molecule of claim 1, which is selected from the group consisting of:

a) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof; and

b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2.

3. The nucleic acid molecule of claim 1 further comprising vector nucleic acid sequences.

4. The nucleic acid molecule of claim 1 further comprising nucleic acid sequences encoding a heterologous polypeptide.

5. A host cell which contains the nucleic acid molecule of claim 1.

6. The host cell of claim 5 which is a mammalian host cell.

7. A nonhuman mammalian host cell containing the nucleic acid molecule of claim 1.

8. A method for producing a polypeptide selected from the group consisting of:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;

b) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:2, wherein the fragment has a kinase protein activity and comprises at least 75 contiguous amino acids of SEQ ID NO:2; and

c) a variant of the polypeptide comprising the amino acid sequence of SEQ ID NO:2, said variant having a kinase protein activity, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof under stringent conditions, said stringent conditions comprising hybridization in 6.times.SSC at 42.degree. C., followed by washing with 1.times.SSC at 55.degree. C.;

comprising culturing the host cell of claim 5 under conditions in which the nucleic acid molecule is expressed.

9. The method of claim 8, wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:2.

10. A method for detecting the presence of a nucleic acid molecule in a sample, comprising the steps of:

a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to said nucleic acid molecule, wherein said nucleic acid probe or primer comprises the nucleic acid molecule of claim 1; and

b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.

11. The method of claim 10, wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.

12. An isolated nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof.

13. The nucleic acid molecule of claim 12 further comprising vector nucleic acid sequences.

14. The nucleic acid molecule of claim 12 further comprising nucleic acid sequences encoding a heterologous polypeptide.

15. A host cell which contains the nucleic acid molecule of claim 12.

16. The host cell of claim 15 which is a mammalian host cell.

17. A nonhuman mammalian host cell containing the nucleic acid molecule of claim 12.

18. An isolated nucleic acid molecule comprising a nucleic acid sequence which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2.

19. The nucleic acid molecule of claim 18 further comprising vector nucleic acid sequences.

20. The nucleic acid molecule of claim 18 further comprising nucleic acid sequences encoding a heterologous polypeptide.

21. A host cell which contains the nucleic acid molecule of claim 18.

22. The host cell of claim 21 which is a mammalian host cell.

23. A nonhuman mammalian host cell containing the nucleic acid molecule of claim 18.

24. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide having a kinase protein activity and which is at least 85% identical to the nucleotide sequence of SEQ ID NO:1, nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof.

25. The nucleic acid molecule of claim 24 further comprising vector nucleic acid sequences.

26. The nucleic acid molecule of claim 24 further comprising nucleic acid sequences encoding a heterologous polypeptide.

27. A host cell which contains the nucleic acid molecule of claim 24.

28. The host cell of claim 27 which is a mammalian host cell.

29. A nonhuman mammalian host cell containing the nucleic acid molecule of claim 24.

30. An isolated nucleic acid molecule comprising a fragment of at least 325 nucleotides of the nucleotide sequence of SEQ ID NO:1 or a complement thereof, wherein said fragment encodes a polypeptide having a kinase protein activity.

31. The nucleic acid molecule of claim 30 further comprising vector nucleic acid sequences.

32. The nucleic acid molecule of claim 30 further comprising nucleic acid sequences encoding heterologous polypeptide.

33. A host cell which contains the nucleic acid molecule of claim 30.

34. The host cell of claim 33 which is a mammalian host cell.

35. A nonhuman mammalian host cell containing the nucleic acid molecule of claim 30.

36. An isolated nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment has a kinase protein activity and comprises at least 75 contiguous amino acids of SEQ ID NO:2.

37. The nucleic acid molecule of claim 36 further comprising vector nucleic acid sequences.

38. The nucleic acid molecule of claim 36 further comprising nucleic acid sequences encoding a heterologous polypeptide.

39. A host cell which contains the nucleic acid molecule of claim 36.

40. The host cell of claim 39 which is a mammalian host cell.

41. A nonhuman mammalian host cell containing the nucleic acid molecule of claim 36.

42. A nucleic acid molecule which encodes a variant of the polypeptide comprising the amino acid sequence of SEQ ID NO;2, said variant having a kinase protein activity, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof, under stringent conditions, said stringent conditions comprising hybridization in 6.times.SSC at 42.degree. C., followed by washing with 1.times.SSC at 55.degree. C.

43. The nucleic acid molecule of claim 42 further comprising vector nucleic acid sequences.

44. The nucleic acid molecule of claim 42 further comprising nucleic acid sequences encoding a heterologous polypeptide.

45. A host cell which contains the nucleic acid molecule of claim 42.

46. The host cell of claim 45 which is a mammalian host cell.

47. A nonhuman mammalian host cell containing the nucleic acid molecule of claim 42.

48. A method for producing a polypeptide comprising the amino acid sequence of SEQ ID NO:2, said method comprising culturing the host cell of claim 15 under conditions in which the nucleic acid molecule is expressed.

49. A method for producing a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:2, wherein the fragment has a kinase protein activity and comprises at least 75 contiguous amino acids of SEQ ID NO:2 and, said method comprising culturing the host cell of claim 39 under conditions in which the nucleic acid molecule is expressed.

50. A method for producing a variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, said variant having a kinase protein activity, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, nucleotides 191-1156 of SEQ ID NO:1, or a complement thereof under stringent conditions, said stringent conditions comprising hybridization in 6.times.SSC at 42.degree. C., followed by washing with 1.times.SSC at 55.degree. C.; said method comprising culturing the host cell of claim 45 under conditions in which the nucleic acid molecule is expressed.