Figure 2: Schematic representation of the Ras-Raf-MAPK mitogenic signaling pathway. This cascade is activated in normal cells when ligand (a growth factor such as platelet-derived growth factor) binds its cognate surface receptor (STEP 1). Ligand:receptor interaction results in receptor dimerization (STEP 2), resulting in transautophosphorylation of tyrosine residues on the intracellular domain of the receptor (STEP 3). This allows signaling molecules with SH2 domains (Shc, Grb2 or the Shc:Grb2 complex) to interact with the phosphotyrosine residues, bringing the nucleotide exchange factor Sos in proximity to the cell surface, where it exchanges GDP with GTP, activating Ras. Raf interacts with activated Ras•GTP, phosphorylating MAPKK, which subsequently phosphorylates MAPK. MAPK translocates to the nucleus where it participates with other molecules in activating the transcription of the transcription factors fos and jun, resulting in the increased transcription of genes involved in cell division and other functions (STEP 4).

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