Critical sites for the interaction between IL-2R gamma and JAK3 and the following signaling

JAK3 is the only known protein tyrosine kinase associating with IL-2R gamma . This interaction is supposed to be very important to IL-2 signaling. In o rder to identify the critical residues for these two molecular interactions and the following signal events, various mutants of gammac and JAK3 were c onstructed on the basis of computer analysis. The direct interaction was de termined via the yeast two-hybrid system, while the signaling was analyzed with reporter genes under the control of the c-fos, c-myc, or tnf-beta prom oters, respectively. Results showed that there are two key sites on gammac involved in this interaction and the following signal transduction: the cri tical one is E327 via electrostatic interaction, the other is L293 via hydr ophobic interaction. As to JAK3, the data indicated that Y100 is important for the interaction with gammac. These results also document that the requi rement for interaction between gammac and JAK3 is different to activate dif ferent signaling pathways mediated by gammac, such as c-fos, c-myc, and JAK -STAT. (C) 2001 Academic Press.