Jak kinases and regulation of cytokine signal transduction

摘要

The present invention is based on the discovery that a critical step in the cellular response to several cytokines is the activation (i.e. tyrosine phosphorylation) of a member of the Jak kinase family. In particular, several cytokines whose activity is mediated by the activation of Jak2 kinase are identified. The present invention provides novel methods for regulating the cellular response to these cytokines by inhibiting or enhancing the Jak kinase activity which mediates the response. Assays for identifying inhibitors of Jak kinase activity or cytokine-induced Jak kinase activation useful in the methods of the invention are also provided. Antibodies raised against peptide fragments of Jak1, Jak2, and Tyk2 kinase capable of specifically binding to these Jak kinases without interfering with kinase activity are also provided. In addition, the complete DNA coding sequence and amino acid structure of Jak2 kinase is provided by the invention.