JAKS, STATS AND SIGNAL-TRANSDUCTION IN RESPONSE TO THE INTERFERONS AND OTHER CYTOKINES

The isolation and complementation of mutant human cell lines has estab lished an essential role for the JAK (Janus kinase) family of protein tyrosine kinases and STAT (signal transduction and transcription) fact ors in the Interferon response pathways. activation of STATs by JAKs o ccurs in receptor complexes at the cell membrane. activated STATs form homo- or heterodimers and, with or without additional factors, migrat e to the nucleus to initiate transcription. Different STAT combination s interact differentially with related DNA response elements. Signalli ng pathways of this novel type are likely utilized by a wide variety o f polypeptide ligands. Data from the IL2, IL6 and IFN systems indicate a major role for the tyrosine phosphorylated receptor/JAK complexes ( rather than substrate specificity of the JAKs per se) in STAT selectio n. The mutant cell lines lacking individual JAKs and STATs are being u sed together with kinase-negative JAK mutants which differentially aff ect the IFN-gamma, and IFN-alpha beta and IL-6 pathways in the further analysis of these and additional systems.