Ruolo della protein chinasi C nella via di trasduzione del segnale Jak-STAT indotta dall'Interferone alfa

The cytokine-activated Janus Kinase (JAK)- Signal Transducer and Activator of Transcription (STAT) pathway is the principal signalling mechanism for a wide array of cytokines and growth factors. JAK activation stimulates cell proliferation, differentiation, cell migration and apoptosis. Dysregulation of JAK- STAT signalling is associated with various pathological disorders. The signalling strength, kinetics and specificity of the JAK- STAT pathway are modulated at many levels by distinct regulatory proteins. Recently, different PKC isoforms have been implied in the regulation of proteins involved in Jak-STAT pathway. In my laboratory is been demonstrated that inhibition of cPKC activity impairs STAT activation and IFN-alpha±- induced gene expression. Here, I reported that cPKC activation is generally required for JAK-STAT signalling pathway activation. Moreover, I shown evidences for a direct regulation of the JAKs activity by cPKC through conformational modification via phosphorylation in the pseudokinase domain.