CELL DIVISION RESPONDS TO EXTERNAL SIGNALS
A large number of extracellular growth factors and hormones exist. Many are specific for particular cells or tissues; for example, epidermal growth factor (EGF) stimulates epithelial cells and fibroblast growth factor (FGF) stimulates muscle cells. Growth factors are bound by specific cell surface receptors. Binding activates the inner domain of the receptor, which is often a protein kinase itself or else activates an associated protein kinase (Fig. 18.5). Typically, the protein kinase activates a protein of the Ras family and this in turn stimulates a phosphotransfer cascade. This consists of three mitogen-activated protein (MAP) kinases. MAP kinase kinase kinase (MAPKKK) activates MAP kinase kinase (MAPKK), which activates MAP kinase (MAPK). Finally, MAPK phosphorylates transcription factors that activate genes needed early in cell division, including the gene for cyclin D.
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