Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease
Patent
1998-05-21
2000-01-11
Achutamurthy, Ponnathapu
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Transferase other than ribonuclease
4353201, 435325, 4352523, C12N 912, C12N 1500, C12N 500, C12N 120
Patent
active
06013500&
ABSTRACT:
This invention provides an isolated mammalian nucleic acid molecule encoding a PAK4 serine/threonine kinase. This invention provides an isolated nucleic acid molecule encoding a mutant homolog of the mammalian PAK4 serine/threonine kinase whose amino acid sequence is set forth in FIG. 1A (SEQ ID NO: 2). This invention provides a fusion protein comprising a PAK4 serine/threonine kinase or a fragment thereof and a second peptide. This invention provides a purified mammalian PAK4 serine/threonine kinase. This invention provides a protein comprising substantially the amino acid sequence set forth in FIG. 1A. This invention provides a monoclonal antibody directed to an epitope of a PAK4 serine/threonine kinase. This invention provides a method of inhibiting PAK4 function comprising administering a ligand comprising an amino acid domain which binds to a GTP binding protein so as to inhibit binding of the GTP binding protein to PAK4. This invention provides a method of inhibiting PAK4 function comprising administering a ligand which binds to the GTP binding domain of PAK4 so as to inhibit PAK4 binding to a GTP binding protein. This invention provides a method of inhibiting PAK4 serine/threonine kinase function comprising administering a ligand which blocks an ATP binding domain so as to inhibit PAK4 serine/threonine kinase function. This invention provides a method of inhibiting growth of a tumor cell comprising blocking Cdc42Hs by administering a ligand capable of binding to a Cdc42Hs binding site of a PAK4 serine/threonine kinase.
REFERENCES:
GenBank Accession No. AF005046, Melnick M.M., submitted May 21, 1997 released to public database on Jan. 15, 1999 (Exhibit 1).
Brown, J. L. et al., (1996) "Human Ste20 Homologue hPAK1 Links GTPases to the JNK MAP Kinase Pathway," Curr. Biol., 6(5):598-605 (Exhibit 1).
Cvrckova, F. et al., (1995) "Ste20-like Protein Kinases Are Required for Normal Localization of Cell Growth and for Cytokinesis in Budding Yeast," Genes. & Dev., 9:1817-1830 (Exhibit 2).
Erickson, J. W. et Al., (1996) "Mammalian Cdc42 Is a Brefeldin A-sensitive Component of the Golgi Apparatus," J. Biol. Chem., 271(43):26850-26854 (Exhibit 3).
Manser, E. et al., (1994) "A Brain Serine/Threonine Protein Kinase Activated by Cdc42 and Rac1," Nature, 367(6458):40-46 (Exhibit 4).
Martin, G. A. 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 (Exhibit 5).
Sells, M. A., and Chernof, J., (1997) "Emerging from the Pak: the p21-activated Protein Kinase Family," Trends Cell. Biol., 7:162-167 (Exhibit 6).
Sells, M. A. et al., (1997) "Human p21-activated Kinase (Pak1) Regulates Actin Organization in Mammalian Cells," Curr. Biol., 7(3):202-210 (Exhibit 7).
Achutamurthy Ponnathapu
Monshipouri M.
The Trustees of Columbia University in the City of New York
White John P.
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