Abstract
Successful use of growth factors in therapeutic and bioprocessing applications requires overcoming two attenuation mechanisms: growth factor depletion and receptor down-regulation. Current ameliorative strategies use physiologically inappropriate high growth-factor concentrations, along with periodic media refeeding in vitro and reinjection or controlled-release devices in vivo. We demonstrate a new approach derived from understanding how these attenuation mechanisms arise from ligand/receptor trafficking processes. Specifically, a recombinant epidermal growth factor (EGF) mutant with reduced receptor binding affinity is a more potent mitogenic stimulus for fibroblasts than natural EGF or transforming growth factor alpha because of its altered trafficking properties.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Cell Division / drug effects
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Down-Regulation / drug effects
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Epidermal Growth Factor / biosynthesis*
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Epidermal Growth Factor / genetics
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / metabolism
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Fibroblasts / drug effects
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics*
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Genetic Engineering
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Mice
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Mitogens / biosynthesis*
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Mitogens / genetics
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Mitogens / pharmacology
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Mutation / genetics
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Recombinant Proteins / genetics
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Signal Transduction / drug effects
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Transforming Growth Factor alpha / genetics
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Transforming Growth Factor alpha / pharmacology
Substances
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Mitogens
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Recombinant Proteins
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Transforming Growth Factor alpha
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Epidermal Growth Factor
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ErbB Receptors