Abstract
Granulocyte/macrophage colony-stimulating factor-interleukin 3 (GM-CSF-IL-3) fusion proteins were generated by construction of a plasmid in which the coding regions of human GM-CSF and IL-3 cDNAs were connected by a synthetic linker sequence followed by subsequent expression in yeast. Both GM-CSF-IL-3 and IL-3-GM-CSF fusion proteins were purified to homogeneity and shown to bind to cell-surface receptors through either their GM-CSF or IL-3 domains. The fusion proteins exhibited enhanced receptor affinity, proliferative activity, and hematopoietic colony-stimulating activity compared with either IL-3 and/or GM-CSF alone. This suggests that GM-CSF-IL-3 fusion proteins may hold future promise as therapeutic agents.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Binding, Competitive
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Cloning, Molecular
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Colony-Forming Units Assay
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Dose-Response Relationship, Drug
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Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
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Granulocyte-Macrophage Colony-Stimulating Factor / chemistry
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Hematopoiesis / drug effects*
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Humans
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In Vitro Techniques
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Interleukin-3 / administration & dosage*
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Interleukin-3 / chemistry
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Molecular Sequence Data
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Oligonucleotides / chemistry
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Protein Conformation
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Receptors, Interleukin-3 / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / pharmacology*
Substances
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Interleukin-3
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Oligonucleotides
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
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Receptors, Interleukin-3
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Recombinant Fusion Proteins
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Granulocyte-Macrophage Colony-Stimulating Factor