Pak kinase genes and polypeptides and methods of use thereof

Details Pak kinase genes and polypeptides and methods of use thereof Pak kinase genes and polypeptides and methods of use thereof

C - Chemistry, Metallurgy

12

N

C12N 15/54 (2006.01) A61K 38/45 (2006.01) A61K 48/00 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12N 9/12 (2006.01) C12N 15/09 (2006.01) C12N 15/63 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2294752

The invention is generally directed to the construction of Pak kinase genes, and to polypeptides encoded by such genes. More specifically, the invention relates to isolated nucleic acid molecules encoding Pak kinase polypeptides wherein the Pak kinases contain a kinase domain and wherein the Pak kinase polypeptides are substantially catalytically inactive, including but not limited to Pak kinase mutants such as the Pak1 kinase mutants Pak1R299, Pak1L83,L86 and Pak1L83,L86,R299. The invention also concerns polypeptides encoded by these isolated nucleic acid molecules and antibodies that specifically bind to these polypeptides. The invention also relates to methods of inhibiting animal cell transformation (particularly that mediated through the activity of the Ras oncogene), and to methods of treating or preventing physical disorders, including cancers and neurological disorders such as neurofibromatosis, in animals (particularly humans) using the mutant Pak kinase genes of the invention. The invention also relates to methods of identifying compounds that modulate the activity of Pak kinases, and to methods of identifying novel Pak kinase targets.

L'invention concerne généralement la construction de gènes de kinases Pak et des polypeptides codés par lesdits gènes. Elle se rapporte, plus spécifiquement, à des molécules d'acide nucléique isolées codant les polypeptides de kinases Pak, les kinases Pak contenant un domaine kinase et les polypeptides de kinase Pak étant sensiblement inactifs du point de vue catalytique, lesdites molécules pouvant être, entre autres, les mutants de kinase Pak1 comme Pak1?R299¿, Pak1?L83,L86¿ et Pak1?L83,L86,R299¿. L'invention porte encore sur des polypeptides codés par ces molécules d'acide nucléique isolées et sur des anticorps qui se lient spécifiquement à ces polypeptides. Elle concerne aussi des procédés d'inhibition de la transformation cellulaire animale (notamment celle induite par l'activité de l'oncogène Ras), et sur des procédés de traitement ou de prévention de troubles physiques, dont les cancers et les troubles neurologiques comme la neurofibromatose, chez les animaux (en particulier les humains), au moyen des gènes mutants des kinases Pak. Elle se rapporte enfin à des procédés d'identification de composés qui modulent l'activité des kinases Pak et à des procédés d'identification de nouvelles cibles des kinases Pak.

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