FUNCTIONAL REGIONS OF THE MOUSE INTERLEUKIN-10 RECEPTOR CYTOPLASMIC DOMAIN

The functions of wild-type and mutant mouse interleukin-10 receptors ( mIL-10R) expressed in murine Ba/F3 cells were studied. As observed pre viously, IL-10 stimulates proliferation of IL-10R-expressing Ba/F3 cel ls, Accumulation of viable cells in the proliferation assay is to a si gnificant extent balanced by concomitant cell death, Moreover, growth in IL-10 also induces a previously unrecognized response, differentiat ion of the cells, as evidenced both by formation of large clusters of cells in cultures with IL-10 and by induction or enhancement of expres sion of several cell surface antigens, including CD32/16, CD2, LECAM-1 (v-selectin), and heat-stable antigen, Two distinct functional region s near the C terminus of the mIL-10R cytoplasmic domain which mediate proliferation were identified; one of these regions also mediates the differentiation response, A third region proximal to the transmembrane domain was identified; removal of this region renders the cell 10- to 100-fold more sensitive to IL-10 in the proliferation assay, In cells expressing both wild-type and mutant IL-10R, stimulation with IL-10 l eads to tyrosine phosphorylation of the kinases JAK1 and TYK2 but not JAK2 or JAK3 under the conditions tested.