Enhanced hematopoietic activity of a human granulocyte/macrophage colony-stimulating factor-interleukin 3 fusion protein

Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5809-13. doi: 10.1073/pnas.88.13.5809.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding, Competitive
  • Cloning, Molecular
  • Colony-Forming Units Assay
  • Dose-Response Relationship, Drug
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / chemistry
  • Hematopoiesis / drug effects*
  • Humans
  • In Vitro Techniques
  • Interleukin-3 / administration & dosage*
  • Interleukin-3 / chemistry
  • Molecular Sequence Data
  • Oligonucleotides / chemistry
  • Protein Conformation
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Receptors, Interleukin-3 / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Interleukin-3
  • Oligonucleotides
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptors, Interleukin-3
  • Recombinant Fusion Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor