Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease
Patent
1997-01-10
1997-12-16
Wax, Robert A.
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Transferase other than ribonuclease
C12N 912
Patent
active
056984286
ABSTRACT:
A novel human serine protein kinase, human p21-protein activated serine kinase p65 protein, referred to as hPAK65, and methods for its preparation and use are provided. Nucleic acids encoding hPAK65 and methods for their use in preparing hPAK65 as well as in preparing and identifying hPAK65 analogs are provided. Methods provided for the use of hPAK65 protein and its protein fragments, such as those that retain at least one hPAK65 activity, that include screening libraries of agents for candidates that modulate hPAK65 activity. Methods are provided to identify agents that modulate the interaction of hPAK65 with rho-like p21 GTPases, particularly rac1 and CDC42Hs binding to hPAK65 and subsequent activation of hPAK65 serine protein kinase activity, that modulate hPAK65 serine protein kinase activity, and that modulate hPAK65 effect on p21 protein GTPase activity. Such modulating agents can provide novel chemotherapeutic agents for treatment of neoplasia, lymphoproliferative conditions, arthritis, inflammation, autoimmune diseases, apoptosis, and the like, that are related to hPAK65 and p21 protein signal transduction pathways.
REFERENCES:
Jakobi et al. (1996) Molecular Cloning and Sequencing of the Cytostatic G Protein-activated Protein Kinase PAKI. J. Biol. Chem. 271(11):6206-6211.
Manser et al. (1994) A Brain Serine/Threonine Protein Kinase Activated by Cdc42 and Rac1. Nature 367:40-46.
Martin et al. (1995) A Novel Serine Kinase Activated by Rac1/CDC42Hs-dependent Autophosphorylation Is Related to PAK65 and STE20. EMBO J. 14(9): 1970-1978.
Teo et al. (1995) Identification and Molecular Cloning of a p21-cdc42/rac1-activated Serine/Threonine Kinase That Is Rapidly Activated by Thrombin in Platelets. J. Biol. Chem. 270(44):26690-26697.
Abo Arie
Martin George A.
Ashton Nina M.
Giotta, Ph.D. FI Onyx Pharmaceuticals Inc. Gregory J.
Hobbs Lisa J.
ONYX Pharmaceuticals, Inc.
Wax Robert A.
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