Journal of Biological Chemistry
Volume 284, Issue 39, 25 September 2009, Pages 26377-26384
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Mechanisms of Signal Transduction
New Activation Modus of STAT3: A TYROSINE-LESS REGION OF THE INTERLEUKIN-22 RECEPTOR RECRUITS STAT3 BY INTERACTING WITH ITS COILED-COIL DOMAIN*

https://doi.org/10.1074/jbc.M109.007955Get rights and content
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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.

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*

This work was supported in part by the Belgian Federal Service for Scientific Technical and Cultural Affairs and the Actions de Recherche Concertées, Communauté Française de Belgique, Direction de la Recherche Scientifique.

1

Research associate of the Fonds National de la Recherche Scientifique, Belgium.