PAK2: modulators of lymphocyte activation
AssigneeRigel Pharmaceuticals, Inc.
InventorsX. Charlene Liao, Peter Chu, Jorge Pardo, Congfen Li, Haoran Zhao, Jun Wu
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Abstract
The present invention relates to regulation of lymphocyte activation. More particularly, the present invention is directed to nucleic acids encoding PAK2, which is involved in modulation of lymphocyte activation. The invention further relates to methods for identifying and using agents, including small organic molecules, peptides, circular peptides, antibodies, lipids, antisense nucleic acids, and ribozymes, that modulate lymphocyte activation via modulation of PAK2; as well as to the use of expression profiles and compositions in diagnosis and therapy related to lymphocyte activation and suppression.
Claims12
A method for identifying a compound that modulates PAK2-mediated T lymphocyte activation, the method comprising the steps of:
- (i) contacting a host T cell comprising a PAK2 polypeptide having serine/threonine kinase activity with the compound, the PAK2 polypeptide encoded by a nucleic acid that hybridizes under stringent conditions to the complement of the nucleic acid encoding a polypeptide having an amino acid sequence of SEQ ID NO:2, wherein the stringent conditions comprise incubating at 42° C. in a solution comprising 50% formamide, 5x SSC, and 1% SDS and washing at 65° C. in a solution comprising 0.2×SSC and 0.1% SDS;
- (ii) activating the host T cell via a T cell receptor (TCR-CD3) and determining whether the compound modulates the TCR-CD3 signaling cascade in the host T cell;
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- (iii) determining whether the compound modulates PAK2 activity, whereby modulation of PAK2 activity and modulation of TCR-CD3 signaling cascade indicates the compound modulates PAK2-mediated T lymphocyte activation.
Dependencies are inferred from the claim text.