A SINGLE STAT RECRUITMENT MODULE IN A CHIMERIC CYTOKINE RECEPTOR COMPLEX IS SUFFICIENT FOR STAT ACTIVATION

We established a system of receptor chimeras that enabled us to induce heterodimerization of different cytoplasmic tails, Fusion constructs were created that are composed of the extracellular parts of the inter leukin-5 receptor alpha and beta chains, respectively, and the transme mbrane and intracellular parts of gp130, the signal transducing chain of the interleukin-6 receptor complex, In COS-7 transfectants we obser ved a dose-dependent interleukin-5-inducible STAT1 activation for whic h the presence of both the alpha and the beta chain chimera was needed , No STAT activity was detected if one of the cytoplasmic tails of the receptor complex was deleted, indicating that STAT activity resulted from a receptor dimer rather than from higher receptor aggregates. We further investigated whether dimerization of STAT1 depends on the juxt aposition of two STAT recruitment modules in a receptor complex, We sh ow that a receptor dimer with only a single STAT1 docking site was sti ll able to lead to STAT1 activation, This indicates that the formation of a paired set of STAT binding sites in a receptor complex is not th e prerequisite for STAT factor dimerization, Our findings are discusse d in view of alternative STAT dimerization models.