Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Knockout of IL-17RB diminishes IL-17B signaling.
  • Fig. S2. Mutation of tyrosine-447 of IL-17RB abrogates IL-17B–induced signaling.
  • Fig. S3. IHC images of primary and metastatic pancreatic tumor specimens using anti–P-Y447 antibody.
  • Fig. S4. Depletion of AAK1, HIPK1, or Syk does not alter IL-17B–induced ERK1/2 phosphorylation.
  • Fig. S5. Knockdown of MLK4 expression reduces IL-17B–induced ERK1/2 phosphorylation, CCL20 and TFF1 expression, and invasion ability of pancreatic and breast cancer cells.
  • Fig. S6. IL-17B, but not IL-17E, induces IL-17RB tyrosine phosphorylation, and FNmut IL-17RB fails to homodimerize.
  • Fig. S7. Overexpression of IL-17RA or treating with IL-17E reduces IL-17B–mediated IL-17RB dimerization and tyrosine phosphorylation.
  • Fig. S8. IL-17B–induced IL-17RB dimerization was not affected by knockdown of TRIM56, MLK4, or mutations of Y447 and K470 of IL-17RB.
  • Fig. S9. CEP-1347 inhibits IL-17RB Y447 phosphorylation, ERK1/2 phosphorylation, and invasiveness of both pancreatic and breast cancer cells.
  • Fig. S10. Predicted structure of the SEFIR domain of human IL-17RB and the steric conformation of Y447.
  • Fig. S11. TRIM56 binds to N458-V462 of IL-17RB and is critical for IL-17RB signaling in vitro.
  • Fig. S12. TRIM56 serves as an E3 ligase for K63-linked ubiquitination of IL-17RB.
  • Fig. S13. Treatment with loop peptide suppresses invasiveness and colony forming in pancreatic tumor cells in vitro.
  • Fig. S14. Loop peptide does not suppress IL-17E–induced IL-4 and IL-13 mRNA expression in peripheral blood mononuclear cells or affect bone marrow–derived dendritic cell activation.
  • Fig. S15. Treatment with loop peptide reduces the recruitment of myeloid-derived suppressor cells and M2 macrophages.
  • Fig. S16. Disruption of the IL-17RB and MLK4 interaction by loop peptide treatment suppresses pancreatic tumor progression.
  • Fig. S17. Graphical summary.
  • Table S1. Univariate and multivariate Cox regression analysis of the influence of IL-17RB phosphorylation on overall survival.
  • Table S2. Phosphorylation of residue Y447 of IL-17RB in pancreatic tumor specimens correlates with worse clinical progression.
  • Table S3. List of proteins interacting with IL-17RB after IL-17B treatment.
  • Table S4. List of proteins coimmunoprecipitated with wild-type IL-17RB, but not Y447F-mutant IL-17RB, after IL-17B treatment.
  • Table S5. List of the primers used in this paper.

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Individual-level data.