Abstract
Single-chain insulin/IGF-1 hybrid-[Ins/IGF-1(C)], single-chain porcine insulin precursor-(PIP), and B10Asp PIP were prepared by protein engineering. Their growth-promoting activities in mouse breast cancer cell line GR2H6 are 10, 0.2, and 2 times that of insulin, respectively, and 29%, 0.6%, and 6% of that of IGF-1, indicating that the C domain and 9Glu of IGF-1 are important for its growth-promoting activity. Given these results and previous reports, we propose that the C domain, 9Glu, and 23Phe-26Asn beta bend are involved in the growth-promoting functional region of IGF-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Division / drug effects
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Chromatography, Agarose
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Dose-Response Relationship, Drug
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Electrophoresis, Polyacrylamide Gel
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Female
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Humans
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Insulin / chemistry
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Insulin / genetics
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Insulin / metabolism*
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Insulin-Like Growth Factor I / chemistry
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism*
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Kinetics
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Mammary Neoplasms, Animal / metabolism
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Mice
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Molecular Sequence Data
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Mutagenesis
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Placenta / metabolism
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Proinsulin / chemistry
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Protein Binding
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Spectrometry, Mass, Electrospray Ionization
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Swine
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Tumor Cells, Cultured
Substances
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Insulin
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Recombinant Fusion Proteins
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Insulin-Like Growth Factor I
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Proinsulin