The p38-MK2-RSK-EphA2 pathway regulates cell migration. HEK293 cells were transfected with the expression vectors for EphA2-KD-EGFP (Ser-897 WT or SA), RSK1-CTKm-FLAG, p38α-CA-FLAG, MK2, and/or an empty vector. At 24 h post-transfection, cells were treated with DMSO or 10 μM BI-D1870 for 2 h (C and D). Whole-cell lysates were immunoblotted with primary antibodies against pS-EphA2, EphA2, FLAG, pMK2, and β-Actin (A and C). Cell migration was observed using a time-lapse imaging system for 120 min (B and D). The accumulated distance of cell migration (μm) was calculated and shown in box and whisker plots. ∗p < 0.05 by the Tukey–Kramer HSD test. EphA2, ephrin type-A receptor 2; MK2, MAPK-activated protein kinase 2; RSK, p90 ribosomal S6 kinase.