LAUSR

HighlightsNDR2 knockdown promotes IL‐17‐induced inflammation by activation of ERK, p38 and NF‐&kgr;B.NDR2 interacts with Smurf1 and MEKK2, and promotes Smurf1‐mediated k48‐linked ubiquitination of MEKK2.MEKK2 positively regulates IL‐17‐induced inflammation while Smurf1 negatively regulates IL‐17‐induced inflammation. Abstract NDR/LATS kinase family are conserved from yeast to man and their roles in inflammation remains largely unknown. In the present study, we show that knockdown of NDR2 significantly increases IL‐17‐induced IL‐6, CXCL2 and CCL20 expression in Hela and HT‐29 cells. Knockdown of NDR2 enhances IL‐17‐induced MAPK and NF‐&kgr;B activation. NDR2 interacts with E3 ubiquitin protein ligase Smurf1, promotes Smurf1‐mediated K48‐linked ubiquitination of MEKK2 and inhibits expression of MEKK2. Consistently, knockdown of Smurf1 increases IL‐17‐induced IL‐6, CXCL2 and CCL20 expression. On the other hand, overexpression of MEKK2 increases IL‐17‐induced IL‐6 expression. These results suggest that NDR2 may play important roles in IL‐17‐associated inflammation by promoting Smurf1‐mediated MEKK2 ubiquitination and degradation.