A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor

Shin Shay Tian, Peter Lamb, Andrew G. King, Stephen G. Miller, Linda Kessler, Juan I. Luengo, Laurie Averill, Randall K. Johnson, John G. Gleason, Louis Pelus, Susan B. Dillon, Jonathan Rosen

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro. It also elevated peripheral blood neutrophil counts in mice. The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464, suggesting that the compound acts by oligomerizing receptor chains. The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand.

Original languageEnglish (US)
Pages (from-to)257-259
Number of pages3
JournalScience
Volume281
Issue number5374
DOIs
StatePublished - Jul 10 1998
Externally publishedYes

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Granulocyte Colony-Stimulating Factor
Granulocyte Colony-Stimulating Factor Receptors
Bone Marrow Cells
Tyrosine
Cultured Cells
Signal Transduction
Proteins
Neutrophils
Phosphorylation
Ligands
SB 247464

ASJC Scopus subject areas

  • General

Cite this

Tian, S. S., Lamb, P., King, A. G., Miller, S. G., Kessler, L., Luengo, J. I., ... Rosen, J. (1998). A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor. Science, 281(5374), 257-259. https://doi.org/10.1126/science.281.5374.257

A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor. / Tian, Shin Shay; Lamb, Peter; King, Andrew G.; Miller, Stephen G.; Kessler, Linda; Luengo, Juan I.; Averill, Laurie; Johnson, Randall K.; Gleason, John G.; Pelus, Louis; Dillon, Susan B.; Rosen, Jonathan.

In: Science, Vol. 281, No. 5374, 10.07.1998, p. 257-259.

Research output: Contribution to journalArticle

Tian, SS, Lamb, P, King, AG, Miller, SG, Kessler, L, Luengo, JI, Averill, L, Johnson, RK, Gleason, JG, Pelus, L, Dillon, SB & Rosen, J 1998, 'A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor', Science, vol. 281, no. 5374, pp. 257-259. https://doi.org/10.1126/science.281.5374.257
Tian SS, Lamb P, King AG, Miller SG, Kessler L, Luengo JI et al. A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor. Science. 1998 Jul 10;281(5374):257-259. https://doi.org/10.1126/science.281.5374.257
Tian, Shin Shay ; Lamb, Peter ; King, Andrew G. ; Miller, Stephen G. ; Kessler, Linda ; Luengo, Juan I. ; Averill, Laurie ; Johnson, Randall K. ; Gleason, John G. ; Pelus, Louis ; Dillon, Susan B. ; Rosen, Jonathan. / A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor. In: Science. 1998 ; Vol. 281, No. 5374. pp. 257-259.
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