DYRK kinases phosphorylate IL-17RA at S801

Abstract

Interleukin-17 (IL-17) receptor A (IL-17RA) promotes inflammatory reactions by activating kinases and transcription regulators. Our previous studies have demonstrated that glycogen synthase kinase 3 (GSK3) phosphorylates IL-17RA at T780. It is not known whether other kinases also phosphorylate IL-17RA. Here, we identified an association between dual‑specificity tyrosine-regulated kinases (DYRKs) and IL-17RA. We found that DYRK1B and DYRK4 interacted with and phosphorylated IL-17RA at serine 801 (S801). Overexpression of DYRK1B and DYRK4 enhanced IL-17RA phosphorylation, whereas siRNA-mediated knockdown of DYRK1B or DYRK4 reduced the phosphorylation. Serum starvation of the cultured cells increased expression levels of DYRK1B/4 and IL-17RA phosphorylation, suggesting stress-dependent modulation of receptor modification. Moreover, selective small‑molecule inhibitors of DYRKs effectively suppressed IL-17RA phosphorylation at S801. Our findings indicate a link between DYRK family kinases and IL-17RA phosphorylation, providing new potential therapeutic targets in the management of IL-17-mediated diseases.