Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Transferases
Patent
1996-03-14
1999-01-26
Wax, Robert A.
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Transferases
435194, 435 691, 4352523, 4353201, 536 232, 530350, 514 2, A61K 3851, C12N 912, C12P 2106, C07H 2104
Patent
active
058635327
ABSTRACT:
The present invention presents a unique class of physiological suppressors of cell division and cleavage. In particular, the present invention presents p21-activated protein kinase PAK I, also known as protease activated protein kinase I (with the same abbreviation "PAK I") which has been purified to apparent homogeneity. PAK I is inactive, e.g. as a protein of about 60 kDa (denoted "p60", as determined by polyacrylamide gel electrophoresis) and is active when autophosphorylated, for example, following limited proteolysis, or binding of Cdc42, e.g., as a protein of about 58 kDa (denoted "p58" as determined by polyacrylamide gel electrophoresis). The present invention also presents a fragment of PAK I, a peptide denoted p37, which contains the catalytic domain of PAK I. The purification, characterization, nucleotide and amino acid sequences of PAK I and p37 are also disclosed. Another aspect of the invention discloses the cytostatic activity of PAK I and its fragments. Further disclosed are the uses of these proteins and peptides for diagnosing and treating diseases, especially for cancer.
REFERENCES:
patent: 5518911 (1996-05-01), Abo et al.
Bagrodia, S., et al., "Identification of a Mouse p21.sup.Cdc42/Rac Activated Kinase", J. Biol. Chem., 270(39):22731-22737 (1995).
Cosco, O. A., et al., "The Small GTP-Binding Proteins Rac1 and Cdc42 Regulate the Activity of the JNK/SAPK Signaling Pathway", Cell, 81:1137-1146 (1995).
Evans, G. A., "Specific Protein Kinases Modulated during T Cell Mitogenesis", J. Biol. Chem., 267(15):10313-10317 (1992).
Fu, X., et al., "Site-specific Phosphorylation of Avian Retrovirus Nucleocapsid Protein pp12 Regulates Binding to Viral RNA", J. Biol. Chem., 260(17):9941-9947 (1985).
Fu, X., et al., "Site-directed Mutagenesis of the Avian Retrovirus Nucleocapsid Protein, pp12, at Serine 40, the Primary Site of Phosphorylation in vivo", J. Biol. Chem., 263(5):2134-2139 (1988).
Hanks, S. K., et al., "The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains", Science, 241:42-52 (1988).
Hanks, S. K., et al., "Protein Kinase Catalytic Domain Sequence Database: Identification of Conserved Features of Primary Structure and Classification of Family Members", Methods Enzymol., 200:38-62 (1991).
Herskowitz, I., "MAP Kinase Pathways in Yeast: For Mating and More", Cell, 80:187-197 (1995).
Jakobi, R., et al., "Human phosvitin/casein kinase type II Molecular cloning and sequencing of full-length cDNA encoding subunit beta", Eur. J. Biochem., 183:227-233 (1989).
Knaus, U. G., et al., "Regulation of Human Leukocyte p21-Activated Kinases Through G Protein--Coupled Receptors", Science, 269:221-223 (1995).
Leberer, E., et al., "The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein .beta..gamma. subunits to downstream signalling components", EMBO J., 11(13):4815-4824 (1992).
Leis, J., et al., "Effects of Phosphorylation of Avian Retrovirus Nucleocapsid Protein pp12 on Binding of Viral RNA", J. Biol. Chem., 259(12):7726-7732 (1984).
Manser, E., et al., "Purification and Assay of Kinases That Interact with Rac/Cdc42", Methods Enzymol., 256:215-227 (1995).
Manser, E., et al., "A brain serine/threonine protein kinase activated by CDC42 and Rac1", Nature, 367:40-46 (1994).
Manser, E., et al., "Molecular Cloning of a New Member of the p21-Cdc42/Rac-activated Kinase (PAK) Family", J. Biol. Chem., 270(42):25070-25078 (1995).
Marcus, S., et al., "Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and mammalian p65.sub.PAK protein kinases, is a component of a Ras/Cdc42 signaling module in the fission yeast Schizosaccharomyces pombe", PNAS (USA), 92:6180-6184 (1995).
Martin, G. A., et al., "A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20",EMBO J., 14(9):1970-1978 (1995).
Meek, W. E., "Protease Activated Kinase 1 (PAK 1) is phosphorylated by Casein Kinase II and Protein Kinase C", FASEB J., 6:A1852 (Abstract 5304) (1992).
Minden, A., et al., "Selective Activation of the JNK Signaling Cascade and c-Jun Transscriptional Activity by the Small CTPases Rac and Cdc42Hs", Cell, 81:1147-1157 (1995).
Mischak, H., et al., "Overexpression of Protein Kinase C-.delta. and -.epsilon. in NIH 3T3 Cells Induces Opposite Effects on Growth, Morphology, Anchorage Dependence, and Tumorigenicity", J. Biol. Chem., 268(9):6090-6096 (1993).
Munemitsu, S., et al., "Molecular Cloning and Expression of a G25K cDNA, the Human Homolog of the Yeast Cell Cycle Gene CDC42", Mol. Cell. Biol., 10(11):5977-5982 (1990).
Nishizuka, Y., "Intracellular Signaling by Hydrolysis of Phospholipids and Activation of Protein Kinase C", Science, 258:607-613 (1992).
Ottilie, S., et al., "Fission yeast pak1.sup.+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating", EMBO J., 14;5908-5919 (1995).
Pendergast, A. M., et al., "Identification of three protein kinases which phosphorylate threonyl-tRNA synthetase from rat liver", FEBS 4091, 206(2):335-337 (1986).
Planas-Silva, M. D., et al., "Expression of a constitutive form of calcium/calmodulin dependent protein kinase II leads to arrest of the cell cycle in G.sub.2 ", EMBO J., 11(2)507-517 (1992).
Prigmore, E., et al., "A 68-kDa Kinase and NADPH Oxidase Component p67.sup.phox Are Targets for Cdc42Hs and Rac1 in Neutrophils", J. Biol. Chem., 270(18):10717-10722 (1995).
Ramer, S. W., et al., "A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae", PNSA (USA), 90:452-456 (1993).
Rooney, R. D., et al., "Identification of Inactive and Active Forms of Protease Activated Protein Kinase I in 3T3-L1 Cells", FASEB J., 6:A1852 (Abstract 5305) (1992).
Rooney, R. D., et al., "Injection of Quiescence Initiating Protein Kinase Into Early Frog Embryos Inhibits Cell Division", FASEB J., 7:A1213 (Abstract 935) (1993).
Sagata, N., et al., "The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs", Nature(London), 342:512-518 (1989).
Shinjo, K., et al., "Molecular cloniung of the gene for the human placental GTP-binding protein G.sub.p (G25K): Identification of this GTP-binding protein as the human homolog of the yeast cell-division cycle protein CDC42", PNAS (USA), 87:9853-9857 (1990).
Tahara, S. M., et al., "Cyclic Nucleotide-Independent Protein Kinases from Rabbit Reticulocytes", J. Biol. Chem., 256(22):11558-11564 (1981).
Tahara, S. M., "Differential Activation of Two Protease-Activated Protein Kinases from Reticulocytes by a Ca.sup.2+ --Simulated Protease and Identification of Phosphorylated Translational Components", Eur. J. Biochem., 126:395-399 (1982).
Teo, M. et al., "Identification and Molecular Cloning of a p21.sup.cdc42/rac1 -activated Serine/Threonine Kinase That is Rapidly activated by Thrombin in Platelets", J. Biol. Chem., 270(44):26690-26697 (1995).
Traugh, J. A., et al., "Isolation of Acetyltransferase Activities from Rabbin Reticulocytes and Modification of Translational Components", Meth. Enzymol., 60:534-541 (1979).
Tuazon, P. T., et al., "Phosphorylation of Myosin Light Chain by a Protease-Activated Kinase from Rabbit Skeletal Muscle", Eur. J. Biochem., 129:205-209 (1982).
Tuazone, P. T., et al., "Activation of Actin-activated ATPase in Smooth Muscle by Phosphorylation of Myosin Light Chain with Protease-activated Kinase I", J. Biol. Chem., 259(1):541-546 (1984).
Tuazon, P. T., et al., "Comparative Analysis of Phosphorylation of Translaional Initiation and Elongation Factors by Seven Protein Kinases", J. Biol. Chem., 264(5):2773-2777 (1989).
Wang, E., "A 57,000-mol-wt Protein Uniquely Present in Nonproliferating Cells and Senescent Human Fibroblasts", J. of Cell Biol., 100:545-551 (1985).
Wang, E., "Disapparence of Statin, a Protein Marker for Non-Proliferating and Senescent Cells, Following Serum-Stimulated Cell Cycle Entry", Experimental Cel. Res., 167:135-143 (1986).
Watanabe, T., et al., "Cell division arrest induced by phorbol ester in CHO cells overe
Carroll, Jr. Edward J.
Chen Charng-Jui
Jakobi Rolf
Meek William E.
Monnig Curtis A.
Saidha Tekchand
The Regents of the University of California
Wax Robert A.
LandOfFree
Compositions and methods comprising cytostatic protein kinase does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions and methods comprising cytostatic protein kinase, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions and methods comprising cytostatic protein kinase will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1447998