Novel nucleic acids and polypeptides which resemble Rho and which interact with cell signalling pathways and proteins
AssigneeOnyx Pharmaceuticals, Inc.
InventorsArie Abo, Ami Aronheim
Life of this patent
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Abstract
The present invention relates to an isolated full-length Chp polypeptide, a biologically-active polypeptide fragment thereof, and nucleic acids which code for it. This polypeptide has various activities in regulating cell signaling and signal transduction pathways, including, e.g., a PAK regulatory domain binding activity, a PAK kinase stimulatory activity, a JNK kinase stimulatory activity, a cytoskeletal-reorganizing activity, or a Chp-specific immunogenic activity. The invention relates to all aspects of Chp, or homologs thereof, including assays for modulators, activators, ligands, etc.
Claims44
An isolated full-length human Chp polypeptide, or a biologically-active polypeptide fragment thereof.
An isolated full-length Chp, or a biologically-active fragment thereof, which is coded for by the complement of a nucleic acid sequence which hybridizes under high stringency conditions to the DNA sequence set forth in FIG. 1 and which has at least 95% sequence identity to said DNA sequence.
An isolated nucleic acid comprising a nucleotide sequence coding for a full-length human Chp polypeptide, or a biologically-active polypeptide fragment thereof.
An isolated nucleic acid which hybridizes under high stringency conditions to the nucleic sequence set forth in FIG. 1, or a complement thereto, and which has at least 95% sequence identity to said nucleic sequence, or its complement.
An isolated nucleic acid consisting essentially of any continuous sequence of 12-100 base pairs, or a complement thereto, selected from the nucleotide sequence set forth in FIG. 1.
A method of identifying compounds which modulate a JNK kinase stimulatory activity or a PAK kinase stimulatory activity of a human Chp polypeptide, or a biologically-active polypeptide fragment thereof, comprising,
- contacting, in the presence of a test compound, a human Chp polypeptide, or a biologically-active polypeptide fragment thereof, with a JNK or PAK polypeptide, or a biologically-active polypeptide fragment thereof, under conditions effective for said Chp polypeptide to stimulate kinase activity of JNK or PNK;
- detecting said kinase activity;
- and
- identifying whether the test compound modulates said stimulatory activity of said Chp polypeptide by comparing the amount of kinase activity in the presence and absence of the test compound.
A method of isolating a compound that modulates the binding between a human Chp and a PakR regulatory domain, comprising:
- contacting a human Chp polypeptide, or a biologically-active polypeptide fragment thereof, with a test compound under conditions effective for said molecule to modulate binding between said Chp polypeptide and said PakR regulatory domain;
- and
- detecting binding between said Chp polypeptide and said PakR regulatory domain in the presence and absence of said test compound.
A method of identifying compounds which modulate a cytoskeletal-reorganizing activity of a human Chp polypeptide, or a biologically-active fragment thereof, comprising:
- introducing an activated form of a human Chp polypeptide, or a biologically-active fragment thereof, into a cell, which polypeptide is effective to stimulate reorganization of said cell's cytoskeleton;
- contacting said cell with a test compound under conditions effective for said compound to modulate said polypeptides effect in stimulating reorganization of said cell's cytoskeleton, whereby such effect is detected by visualizing said cytoskeleton;
- and
- visualizing said cytoskeleton in the presence and absence of said test compound.
An isolated antibody which is specific for a polypeptide sequence of human Chp.
Dependencies are inferred from the claim text.