Fig. 5: MEK mutations generate distinct gene expression patterns.

a Transcriptome analyses of HEK293 cells stably expressing HA-MEK1 WT, F53S, or K57N. Genes differentially expressed between WT and F53S (left), WT and K57N (middle), and F53S and K57 (right) are displayed as volcano plots (x-axis: fold-change [log2], y-axis: p-value [-log10]). Red area, log₂FC > 1 and p < 0.05 (n = 3); blue area, log₂ FC < −1 and p < 0.05 (n = 3). b Venn diagrams illustrating the number of genes significantly upregulated (>2-fold; left) and downregulated (<0.5-fold; right) in F53S and K57N cells vs. WT cells. c Principal component analysis of the gene expression profiles of WT, F53S, and K57N cells. d KEGG pathway enrichment analyses of genes upregulated in F53S and K57N cells vs. WT cells. e Gene sets enriched analysis. The indicated gene signatures were significantly enriched in K57N cells compared with F53S cells. f Five distinct patterns of gene expression relative to the degree of aberrant ERK activity in F53S and K57N cells. (Upper) Schematic representations of the gene expression patterns. (Lower) qRT-PCR analysis of the expression level of a representative gene in each group. Data are mean ± SEM from three independent experiments. P-values were determined using one-way ANOVA followed by Tukey’s multiple comparisons test. ns, not significant. g Immunoblot analysis of representative secreted proteins of the sigmoidal-B group (TFPI2 and GDF15) and the bell-shaped group (COL14A1) in cell culture supernatants from the indicated cells. Source data are provided as a Source Data file.