Abstract: The present invention provides for a stable, biologically active CNTF/receptor complex, and hybrids or mutants thereof. The invention is also based in part on the discovery that the CNTF/receptor complex promotes differentiation through a signal transduction pathway on target cells that do not express the CNTF receptor. The invention further provides for a specific CNTFR mutant that promotes signal transduction without binding CNTF. The invention also provides for a CNTF/receptor blocking mutant, a mutant possessing a high binding affinity to CNTF, but possessing no signal transducing function. The present invention also identifies receptor components shared by the IL-6, CNTF, LIF and OSM signal transduction pathways, and the assay systems based on the use of such components.

Abstract: 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.