Human PAK65

Details Human PAK65 Human PAK65

1998-07-01

2000-04-11

Hobbs, Lisa J.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving transferase

435 78, 435194, 435366, C12Q 148, G01N 3353, C12N 912, C12N 500

Patent

active

060487062

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:
Nobes, C., and Hall, A. (1994) Curr. Opin. Gen. Devel. 4, 77-81.
Hart, M. J., Eva, A., Evans, T., Aaronson, S.A., Cerione, R.A. (1991) Nature 354; 311-314.
Boguski, M.S., McCormick, F. (1993) Nature, 366, 643-654.
Ridley, A.J., Hall, A. (1992) Cell 70, 389-399.
Ridley, A.J., Paterson, H.F., Johnston, C.L. Diekmann, D., Hall, A. (1992) Cell 70, 401-410.
Takaishi, K., Kikuchi, A., Kuroda, S., Kotani, K., Sasaki, T., Takai, Y. (1993), Mol. Cell. Biol. 13, 72-79.
Kishi, K., Sosaki, T., Kuroda, S., Itah, T., Takai, Y. (1993) J. Cell Biol. 120, 1187-95.
Tominaga, T., Sugie, K., Hirata, M., Fukata, J., Uchida, A., Imura, H., Narumiya, S. (1993) J. Biol. Chem. 120, 1529-1537.
Johnson, D., Pringle, J. (1990) J. Cell Biol. 111, 143-152.
Gulbins, E., Coggeshall, K.M., Baier, G., Katzav, S., Burn, P., Altman, A. (1993) Science 260, 822-825.
Miki., T., Smith, C.L., Long, J.E., Eva, A., Flemming, T.P. (1993) Nature 362, 462-465.
Khosravi-Far, R., Chrzanowska-Wodnicka, M., Solski, P.A., Eva, A., Burridge, K., Der, C.J. (1994) Mol. Cell. Biol. 14, 6848-6857.
Abo, A., Pick, E., Hall, A., Totty, N., Teahan, C.G., Segal, A.W. (1991) Nature 353, 668-670.
Knaus, U. G., Heyworth, P.G., Evans, T., Curnutte, J.T., Bokoch, G.. M. (1991) Science 254, 1512-1515.
Segal, A.W., Abo, A. (1993) Trends. Biochem. Sci. 18, 43-47.
Diekmann, D., Abo, A., Johnston, C., Segal, A.W., Hall, A. (1994) Science 265, 531-533.
Manser, E., Leung, T., Salihuddin, H., Zhao, Z., Lim, L. (1994) Nature 367, 40-46.
Zheng, Y., Bagrodia, S., Cerione, R.A. (1994) J. Biol. Chem. 269, 18727-18730.
Zhang, J., King, W.G., Dillon, S., Hall, A., Feig, L., Rittenhouse, S.E. (1993) J. Biol. Chem. 268, 22251-4.
Abo, A., Webb, M. R., Grogan, A., Segal, A.W. Biochem. J. (1994) 298, 585-591.
Kawasaki, H., and Suzuki, K., (1990) Anal. Biochem. 186, 264-268.
Totty, N.F., Waterfield, M.D. , Hsuan, J.J. (1992) Prot. Sci. 1, 1215-1224.
Grussenmeyer, T., Scheidtmann, K.H., Hutchinson, M.A., Eckhart, W., Gernot, W. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7952-7954.
Shacter, E. (1984) Anal. Biochem. 138, 416-420.
Cooper, A.J., Sefton, B.M., Hunter, T. (1983) in Methods in Enzymology 99, 37.
Manser, E., Leung, T., Monfries, C., Teo, M., Hall, C., Lim, L. (1992) J. Biol. Chem. 267, 16025-16028.
Ramer, S.W., and Davis, R.W. (1993) Proc. Nat. Acad. Sci. U.S.A. 90, 452-456.
Avruch, J., Zhang, X., Kyriakis, J. (1994) Trend. Biochem. Sci. 19, 279-284.
Leberer, E., Dignard, D., Harcus, D., Thomas, D.Y., Whiteway, M., (1992b) EMBO J. 11, 4805-4813.
Errede, B., Levin, D.E. (1993) Curr. Opin. Cell Biol. 5, 254-260.
Errede, B., Gartner, A., Zhou, Z., Nasmyth, K., Ammerer, G., (1993), Nature 362, 261-264.
Leberer, E., Dignard, D., Harcus, D., Hougan, L., Whiteway, M., Thomas, D.Y. (1993) Mol. Gen. Genet. 241, 241-254.
Settleman, J., Albright, C.F., Foster, L.C., Weinberg, R. A. (1992) Nature 359, 153-154.
Knaus et al., (1995) Science, 269, 221-223.
Benner et al., Activation of an SH6/H4 Kinase (PAK65) from Human Placenta by Intramolecular and Intermolecular Autophosphorylation, J. Biol. Chem., vol. 270(36) :21121-21128 (1995).
Leberer et al., EMBO J., vol. 11(13) :4815-4824 (1992).
Jakobi et al., Molecular Cloning and Sequencing of the Cytostatic G Protein-activated Protein Kinase PAKI., J. Biol. Chem., vol. 271(11) :6206-6211 (1996).
Martin et al., A Novel Serine Kinase Activated by Rac1/CDC42Hs-dependent Autophosphorylation is Related to PAK65 and STE20., EMBO J., vol. 14 (9) :1970-1978 (1995).
Teo et al., Identification and Molecular Cloning of a p21-cdc42/rac1-activated Serine/Threonine Kinase That is Rapidly Activated by Thrombin in Platelets, J. Biol. Chem., vol. 270(44) :26690-26697 (1995) .

Affiliated with

Also associated with

Rating

Human PAK65 does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Human PAK65, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Human PAK65 will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1175553