PAK KINASE GENES AND POLYPEPTIDES AND METHODS OF USE THEREOF

摘要

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 Pak1<R299>, Pak1<L83,L86> and Pak1<L83,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.