MAP2K4 and cancer: The MAP3K1 and MAP2K4 kinases activate the JUN transcription factor through the JNK kinases.24 JUN in turn activates several RTKs, including EGFR,29–32 HER233 and PDGFRB.34 To study the mechanism of sensitivity of MAP2K4 mutant cancer cells to MEK inhibition, we analyzed ERK and JNK signaling in MAP2K4 mutant and wild-type cells.