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 previously, IL-10 stimulates proliferation of IL-10R-expressing Ba/F3 cells. Accumulation of viable cells in the proliferation assay is to a significant extent balanced by concomitant cell death. Moreover, growth in IL-10 also induces a previously unrecognized response, differentiation of the cells, as evidenced both by formation of large clusters of cells in cultures with IL-10 and by induction or enhancement of expression of several cell surface antigens, including CD32/16, CD2, LECAM-1 (v-selectin), and heat-stable antigen. Two distinct functional regions 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 leads to tyrosine phosphorylation of the kinases JAK1 and TYK2 but not JAK2 or JAK3 under the conditions tested.
Ho
A S
AS
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Wei
S H
SH
Mui
A L
AL
Miyajima
A
A
Moore
K W
KW
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D018801:CD2 Antigens / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D019041:L-Selectin; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D018801:CD2 Antigens; D015815:Cell Adhesion Molecules; D007377:Interleukin-3; D017452:Receptors, IgG; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D019041:L-Selectin; D016753:Interleukin-10; D011505:Protein-Tyrosine Kinases