Illustration of a cell membrane showing the proteins involved in the Raf-MEK-ERK, or MAPK/ERK, pathway. The signal cascade begins when epidermal growth factor (EGF) binds to the EGF receptor on the outside of the cell membrane, activating it and triggering the phosphorylation of tyrosines (red dots) on the intracellular portion of the receptor. Growth factor receptor-bound protein 2 (GRB2) binds to these tyrosines and the guanine nucleotide exchange factor SOS, activating SOS, which stimulates the release of GDP (guanine diphosphate) from RAS. This activates RAS, which activates RAF (rapidly accelerated fibrosarcoma) kinase, which induces a conformational change in KSR (kinase suppressor of Ras), that allows the activation of MEK (mitogen-activated protein kinase). Activated MEK then activates ERK (extracellular signal-regulated kinase), which is transported to the cell nucleus where it activates transcription factors, leading to cell proliferation, survival, and growth. Misregulation of this pathway can lead to cancer. For an unlabelled version of this image see F037/5390.