Figure 1.
Mitogen-activated protein kinase (MAPK) pathway regulates nuclear and cytoplasmic activities. (a) Membrane receptor stimulation activates RAS GTPase which phosphorylates and activates RAF ⟶ MEK ⟶ ERK. BRAF forms homo- or heterodimers with other RAF-family proteins (ARAF or CRAF)∗ leading to MEK activation. BRAFV600E is constitutively active and phosphorylates MEK independent of RAS activation and dimerization. ERK-specific phosphorylation regulates its localization. Cytoplasmic ERK regulates RSK and MNK to modulate cellular function including transcription, proliferation, and invasion. (b) Phosphorylated ERK may phosphorylate RSK, which can translocate to the nucleus. In the nucleus, other transcription factors are recruited to promote expression of growth and prosurvival proteins.