Isolated dishevelled associated kinases, polynucleotides encoding the kinases, and methods of use thereof
AssigneeThe Regents of the University of California
InventorsTian-Qiang Sun, Lewis T. Williams
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Abstract
The invention provides Dishevelled Associated Kinase polypeptides, which phosphorylate Dsh proteins involved in the Wnt/Wg signalling pathway. Isolated polynucleotides encoding DAK polypeptides are further provided, as are recombinant vectors, and host cells comprising the polynucleotides. Methods of using the polynucleotides and polypeptides of the invention are further aspects of the invention, including assays to detect agents which modulate DAK kinase activity. Further provided are methods of modulating pathways involved in control of cell proliferation.
Claims29
An isolated polypeptide comprising at least about 20 contiguous amino acids of the sequence depicted in SEQ ID NO:2 or 4.
An isolated polynucleotide which encodes a polypeptide comprising at least about 6 contiguous amino acids of the sequence depicted in SEQ ID NO:2 or 4.
An isolated polynucleotide comprising a nucleotide sequence which has at least about 70% nucleotide sequence identity to a sequence set forth in SEQ ID NO:1 or 3.
An isolated polynucleotide comprising at least about 18 contiguous nucleotides of the sequence set forth in SEQ ID NO:1 or 3.
An isolated antibody which specifically binds a protein selected from the group consisting of a polypeptide having the sequence depicted in SEQ ID NO:2 and a polypeptide having the sequence depicted in SEQ ID NO:4.
A method of detecting a DAK polypeptide in a sample, comprising:
- a) contacting the sample with an antibody which specifically binds the DAK polypeptide;
- and
- b) detecting binding between the antibody and molecules of the sample.
A method of identifying a substance which modulates a kinase activity of a Dishevelled Associated Kinase (DAK), comprising:
- a) contacting the substance with a sample containing a DAK polypeptide;
- and
- b) assaying a kinase activity of the DAK polypeptide in the presence of the substance, wherein an increase or a decrease in kinase activity in comparison to DAK kinase activity in a suitable control is an indication that the substance modulates a kinase activity of the DAK.
A method of detecting the presence of a Dishevelled Associated Kinase (DAK) messenger RNA (mRNA) molecule in a biological sample, comprising:
- a) contacting the sample with a DAK polynucleotide complementary to DAK mRNA under conditions which allow hybridization;
- and
- b) detecting hybridization, if any.
A method of detecting Dishevelled Associated Kinase (DAK) kinase activity in a biological sample, comprising:
- a) contacting the sample with a Dishevelled protein;
- and
- b) detecting phosphorylation of the Dishevelled protein.
A method of inhibiting binding of a Dishevelled associated kinase (DAK) polypeptide to a Dishevelled (Dsh) polypeptide, comprising:
- contacting a sample comprising a DAK polypeptide and a Dsh polypeptide with a specific inhibitor of DAK-Dsh binding.
A method of reducing a level of β-catenin in the nucleus of a eukaryotic cell, comprising contacting a eukaryotic cell with a substance that enters the cell and inhibits a Dishevelled associated kinase (DAK) kinase activity, thereby reducing β-catenin levels in the nucleus.
Dependencies are inferred from the claim text.