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PMID: 1829529 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 13 ·1991-07-01 ·Pages 5809-13

Curtis BM, Williams DE, Broxmeyer HE, Dunn J, Farrah T, Jeffery E, Clevenger W, deRoos P, Martin U, Friend D

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.

MeSH Terms
Base Sequence Binding, Competitive Cloning, Molecular Colony-Forming Units Assay Dose-Response Relationship, Drug Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage,chemistry Hematopoiesis/drug effects Humans In Vitro Techniques Interleukin-3/administration & dosage,chemistry Molecular Sequence Data Oligonucleotides/chemistry Protein Conformation Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism Receptors, Interleukin-3/metabolism Recombinant Fusion Proteins/chemistry,pharmacology
Chemicals
Interleukin-3 Oligonucleotides Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Receptors, Interleukin-3 Recombinant Fusion Proteins Granulocyte-Macrophage Colony-Stimulating Factor
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Curtis B M
Immunex Research and Development Corporation, Seattle, WA 98101.
Williams D E
Broxmeyer H E
Dunn J
Farrah T
Jeffery E
Clevenger W
deRoos P
Martin U
Friend D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.13.5809
Published
1991-07-01
Pages
5809-13
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51967
Subset
IM
Grants
NCI NIH HHS · R01 CA 36740 · United States
NCI NIH HHS · R37 CA-36464 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.13.5809 PMC Full Text View journal details
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