IL-10 Receptor Rene de Waal Malefyt* Department of Molecular Biology, DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304-1104, USA * corresponding author tel: 650-496-1164, fax: 650-496-1200, e-mail:
[email protected] DOI: 10.1006/rwcy.2000.14005.
SUMMARY IL-10 interacts with its tetrameric receptor complex consisting of two IL-10R and two IL-10R chains resulting in the phosphorylation and activation of JAK1 and TYK2 kinases, which in turn phosphorylate two tyrosine residues in the intracytoplasmic parts of the IL-10R chains that form docking sites for STAT3. Binding of STAT3 results in phosphorylation by JAK1 and TYK2 kinases, homo- or heterodimerization and translocation to the nucleus where it binds to the promoters of IL-10-responsive genes such as the Fc RI and activates transcription. All IL-10-mediated responses are dependent on activation of STAT3, but the anti-inflammatory actions of IL-10 require additional sequences in the distal intracytoplasmic part of the IL-10R chain.