1. New Activation Modus of STAT3: A TYROSINE-LESS REGION OF THE INTERLEUKIN-22 RECEPTOR RECRUITS STAT3 BY INTERACTING WITH ITS COILED-COIL DOMAIN.
- Author
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Dumoutier, Laure, de Meester, Carole, Tavernier, Jan, and Renauld, Jean-Christophe
- Subjects
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INTERLEUKINS , *CYTOKINES , *GLUTATHIONE , *IMMUNOREGULATION , *TYROSINE , *AMINO acids - Abstract
Activation of STAT proteins by cytokines is initiated by their Src homology 2 domain-mediated association with phosphotyrosine residues from the cytoplasmic domain of a receptor. Here, we show that the C terminus of the interleukin-22 receptor (IL-22R) recruits in a tyrosine-independent manner the coiled-coil domain of STAT3. Mutation of all IL-22R cytoplasmic tyrosines did not abolish activation of STAT3, in contrast to that of STAT1 and STAT5. Coimmunoprecipitation and glutathione S-transferase pulldown experiments showed that the coiled-coil domain of STAT3 is constitutively associated with the C-terminal part of IL-22R, and a chimeric STAT3-STAT5 protein containing the coiled-coil domain of STAT3 could be activated by this tyrosine-independent mechanism. Deletion of the C-terminal part of IL-22R dramatically decreased its ability to activate STAT3 and to mediate IL-22 activity in cell lines, demonstrating that preassociation of STAT3 with this cytokine receptor, independent from the interaction between the Src homology 2 domain and phosphotyrosines, is required for its full activity. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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