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Illustration of a cell membrane (purple and orange) 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 which forms a heterodimer (complex of two different molecules) with human epidermal growth factor receptor 3 (HER3). This triggers the phosphorylation of tyrosines (amino acids) 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. This activates SOS, which stimulates the release of GDP (guanine diphosphate) from RAS. This activates RAS, a small protein which in turn activates RAF (rapidly accelerated fibrosarcoma) kinase. RAF kinase 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 (TFs). These TFs activate genes which promote cell proliferation, survival, and growth. Misregulation of this pathway can lead to cancer