“Growth factors are small, soluble proteins or peptides that bind to the extracellular domain of cell receptors and activate signal transduction pathways. Binding of growth factors induces dimerization of receptors and tyrosine autophosphorylation on their cytoplasmic domains. These phosphotyrosines are bound by other proteins and results in formation of large protein complexes. Many of these proteins are phosphorylated by receptors to initiate signal transduction. For example, the EGF receptor activates tyrosine kinase Src and serine/threonine-specific MAP kinase cascades. These cascades cause phosphorylation of several target proteins to activate gene expression that mediates cell growth, proliferation and motility. Absence of growth factors or inhibiting their downstream cascades causes severe cell cycle arrest or cell death.
Activated receptors are taken into endosomes that later fuse with lysosomes causing receptor degradation and termination of signaling, limiting the ability of cells to grow. Studies on growth factor functions are often carried out using mouse growth factor receptor knockout models (note: a knockout model is an organism modified to have the target gene be nonfunctional), and microscopic and biochemical analysis of cells treated with growth factors. Yeast has a well-conserved MAP kinase cascade, but lacks other growth factor signaling pathways conserved in multi-cellular organisms.
Alterations that activate growth factor receptors and confer proliferation and survival advantages are detected in cancers. For example, high levels of EGF receptor are detected in several types of cancers. Several drugs that target these growth receptors are currently being developed or tested against cancers. Gefitinib is an example of an anti-EGF receptor drug used in breast and lung cancer treatments. However, growth factors are necessary for normal cellular functions and these drugs can interfere with them; for example, insufficient activity of EGF receptor is associated with neurodegenerative disorders while the loss of EGF receptor causes defective heart, lung and brain development and embryonic mortality.
Find an error? Take a screenshot, email it to us at firstname.lastname@example.org, and we’ll send you $3!