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https://hdl.handle.net/2440/8985
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Type: | Journal article |
Title: | The interaction of GM-CSF and IL-3 with the common beta chain of their receptors |
Author: | Bagley, C. Woodcock, J. Hercus, T. Shannon, M. Lopez, A. |
Citation: | Journal of Leukocyte Biology, 1995; 57(5):739-746 |
Publisher: | Liss |
Issue Date: | 1995 |
ISSN: | 0741-5400 1938-3673 |
Abstract: | Human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL-3) are cytokines active in both normal and abnormal hemopoiesis, inflammation, and immunity. Their biological activity is mediated via receptors that comprise a ligand-specific alpha chain and a beta chain that is common to the GM-CSF, IL-3, and IL-5 receptors. To understand the mechanism of action of GM-CSF and IL-3 in both normal and pathological conditions, we are seeking to define the structural elements required for ligand/receptor and receptor/receptor contact and their role in cellular activation. To this end we have identified a conserved motif in the first helix of GM-CSF, Glu21 that is critical for high affinity binding and biological activity. Charge-reversal mutagenesis of this residue generates a GM-CSF analogue that is devoid of biological activity and can antagonize the activity of wild-type GM-CSF. This probably results from the selective deficiency in interaction with the beta chain of the receptor and suggests that similar antagonists for IL-3 and IL-5 are also feasible. Complementary mutagenesis studies on the receptor beta chain have identified the putative B'-C' loop in the membrane-proximal domain as being critical for the high affinity binding of GM-CSF but not IL-3. Characterization of the specificity of sites of interaction between the ligands and receptors may permit the design of specific or genetic antagonists that may have important therapeutic implications. |
Keywords: | Humans Growth Hormone Granulocyte-Macrophage Colony-Stimulating Factor Interleukin-3 Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Receptors, Interleukin-3 Sequence Alignment Binding Sites Binding, Competitive Amino Acid Sequence Protein Structure, Secondary Sequence Homology, Amino Acid Structure-Activity Relationship Models, Molecular Molecular Sequence Data |
DOI: | 10.1002/jlb.57.5.739 |
Published version: | http://dx.doi.org/10.1002/jlb.57.5.739 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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