Pak2-mediated phosphorylation promotes RORγt ubiquitination and inhibits colonic inflammation.

ABSTRACT: Dysregulated interleukin-17 (IL-17) expression and its downstream signaling is strongly linked to inflammatory bowel diseases (IBDs). However, the molecular mechanisms by which the function of RORγt, the transcription factor of IL-17, is regulated remains elusive. By a mass spectrometry-based approach, we identify that Pak2, a serine (S)/threonine (T) kinase, directly associates with RORγt. Pak2 recognizes a conserved KRLS motif within RORγt and phosphorylates the S-316 within this motif. Genetic deletion of Pak2 in Th17 cells reduces RORγt phosphorylation, increases IL-17 expression, and induces severe colitis upon adoptive transfer to Rag1^-/- mice. Similarly, reconstitution of RORγt-S316A mutant in Rorc^-/- Th17 cells enhances IL-17 expression and colitis severity. M

SUBMITTER: Kathania M 

PROVIDER: S-EPMC9510046 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature