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, red, top left) binds to the EGF receptor (blue, far left) on the outside of the cell membrane, activating (second from left) it and triggering the phosphorylation of tyrosines (red dots) on the intracellular portion of the receptor. Growth factor receptor-bound protein 2 (GRB2, light blue, lower centre) binds to these tyrosines and the guanine nucleotide exchange factor SOS (purple, centre), activating SOS, which stimulates the release of GDP (guanine diphosphate) from RAS (three at centre right, blue). This activates RAS (light blue, right), which activates RAF (rapidly accelerated fibrosarcoma, dark blue, right) kinase, which induces a conformational change in KSR (kinase suppressor of Ras, dark purple, lower centre right), that allows the activation of MEK (mitogen-activated protein kinase, light purple, lower centre right). Activated MEK then activates ERK (extracellular signal-regulated kinase, orange), 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 a labelled version of this image see F037/5389.