Fig. 6: TYK2-mediated tau phosphorylation at Tyr29 augments tau nitration at Tyr29 in HEK293T cells.
From: TYK2 regulates tau levels, phosphorylation and aggregation in a tauopathy mouse model
a, IB image and quantification of tau phosphorylation and nitration at Tyr29 residue of WT tau441 in the presence of TYK2 or/and CAPON in HEK293T cells. Tau nitration at Tyr29 residue is increased by phosphorylation at the same residue by TYK2 regardless of CAPON expression (n = 4; top-right, one-way ANOVA/Tukey’s multiple comparison, P(Mock versus TYK2) = 0.00334, P(CAPON–Mock versus CAPON–TYK2) = 0.001830, P(Mock versus CAPON–Mock) = 0.011628; bottom-right, unpaired t test/two-tailed, P(Mock versus CAPON) = 0.0921). b, Quantitative graph of tau aggregation from cells treated with DMSO or Zlc002 (CAPON inhibitor, 1 mM), followed by transfection (RFP, TYK2, TYK2KD or/and CAPON) and tau seed transduction (n = 4; two-way ANOVA/Tukey’s multiple comparison test, P(DMSO versus ZLc002) > 0.9999, P(DMSO versus CAPON–DMSO) > 0.9999, P(DMSO versus CAPON–ZLc002) = 0.9999, P(CAPON–DMSO versus CAPON–ZLc002) = 0.9998). Tau aggregation was increased by TYK2 but was not changed by either the CAPON or Zlc002 (n = 4). n is the number of biological repeats. Data are represented as mean ± s.e.m., *P < 0.05, **P < 0.01 and ***P < 0.0005.
