EPHA2 receptor downregulation induced by H. pylori infection is preceded by receptor phosphorylation early on and is followed by lysosomal degradation in the MKN74 gastric cell line. (a) Tyrosine and serine897 phosphorylation of EPHA2 upon H. pylori exposure, as determined by ELISA and Western blot, respectively; *** p < 0.001, ** p < 0.01, * p ≤ 0.05, ns—not significant (p > 0.05). (b) Effect of PP2 (SRC family kinase inhibitor), U0126 (MEK inhibitor), and CAY10626 (PI3Kα/mTOR inhibitor) on downregulation of EPHA2 mediated by H. pylori at 24 h by Western blot and corresponding quantifications by densitometry; **** p < 0.0001, *** p < 0.001, ** p < 0.01, ns—not significant (p > 0.05). (c) Effect of SRC family kinase inhibitors (PP2 and Dasatinib inhibitors) on EPHA2-tyrosine phosphorylation 1 h after H. pylori infection, as evaluated by ELISA; **** p < 0.0001, ** p < 0.01, * p ≤ 0.05. (d) Effect of lysosomal (Bafilomycin A1 and Concanamycin A) and proteasomal (bortezomib) inhibitors on EPHA2 receptor downregulation induced by H. pylori at 24 h post-infection as shown by Western blot and the respective relative density expressed as the ratio of infected/uninfected cells; *** p < 0.001; ** p < 0.01; ns—not significant (p > 0.05). One-way ANOVA with post-hoc Dunnett’s or Tukey’s test.