title: Proteasome-mediated proteolysis of the interleukin-10 receptor is important for signal downregulation.
abstract: The cytokine interleukin-10 (IL-10) is an important regulator of immune cell function, proliferation, and survival. The IL-10 receptor (IL-10R) consists of two subunits, IL-10R1 and IL-10R2, both belonging to the class II cytokine receptor superfamily. Like other members of the cytokine receptor superfamily, IL-10R stimulation leads to activation of Jak family kinases and Stat transcription factors. To identify additional signal transduction pathways used by the IL-10R, we purified 92-kDa and 100-kDa proteins that coprecipitated with IL-10R1 from IL-10-stimulated cells. Both proteins were found to be related to the 97-kDa subunit of the regulatory component of the 26S proteasome. Subsequent studies confirmed that the IL-10R1 undergoes ligand- dependent internalization and proteasome-mediated degradation. An IL-10R1 cytoplasmic domain mutant deficient for internalization exhibited prolonged signaling through Jak1 and Stat3, reinforcing the importance of receptor internalization for signal termination.
authors: DNAX Research Institute, Palo Alto, CA 94304, USA.
authors: Sherry H-Y
authors: SH
authors: Wei
authors: Andrew
authors: A
authors: Ming-Lum
authors: Ying
authors: Y
authors: Liu
authors: David
authors: D
authors: Wallach
authors: Christopher J
authors: CJ
authors: Ong
authors: Stephen W
authors: SW
authors: Chung
authors: Kevin W
authors: KW
authors: Moore
authors: Alice L-F
authors: AL
authors: Mui