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The receptor tyrosine kinases (RTKs) are the second major type of cell-surface receptors. The ligands for RTKs are soluble or membrane-bound peptide/protein hormones including nerve growth factor (NGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin. Binding of a ligand to this type of receptor stimulates the receptor’s intrinsic protein-tyrosine kinase activity, which subsequently stimulates a signal-transduction cascade leading to changes in cellular physiology and/or patterns of gene expression. RTK signaling pathways have a wide spectrum of functions including regulation of cell proliferation and differentiation, promotion of cell survival, and modulation of cellular metabolism. Some RTKs have been identified in studies on human cancers associated with mutant forms of growth-factor receptors, which send a proliferative signal to cells even in the absence of growth factor. One such mutant receptor, encoded at the neu locus, contributes to the uncontrolled proliferation of certain human breast cancers. Other RTKs have been uncovered during analysis of developmental mutations that lead to blocks in differentiation of certain cell types in C. elegans, Drosophila, and the mouse.
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