Kinetic resolution of two mechanisms for high-affinity granulocyte-macrophage colony-stimulating factor binding to its receptor Journal Article
| Authors: | Niu, L.; Golde, D. W.; Vera, J. C.; Heaney, M. L. |
| Article Title: | Kinetic resolution of two mechanisms for high-affinity granulocyte-macrophage colony-stimulating factor binding to its receptor |
| Abstract: | Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic cytokine that exerts its effects by interaction with the GM-CSF receptor (GMR) on the surface of responsive cells. The GM-CSF receptor consists of two subunits: GMRα, which binds GM-CSF with low affinity, and GMRβ, which lacks intrinsic ligand-binding capability but complexes with GMRα to form a high-affinity receptor (GMRα/β). We conducted dynamic kinetic analyses of GM-CSF receptors to define the role of GMRβ in the interaction of ligand and receptor. Our data show that GMRα/β exhibits a higher k(on) than GMRα, indicating that GMRβ facilitates ligand acquisition to the binding pocket. Heterogeneity with regard to GM-CSF dissociation from GMRα/β points to the presence of loose and tight ligand- receptor complexes in high-affinity binding. Although the loose complex has a k(off) similar to GMRα, the lower k(off) indicates that GMRβ inhibits GM- CSF release from the tight receptor complex. The two rates of ligand dissociation may provide for discrete mechanisms of interaction between GM- CSF and its high-affinity receptor. These results show that the β subunit functions to stabilize ligand binding as well as to facilitate ligand acquisition. |
| Keywords: | human cell; binding affinity; granulocyte macrophage colony stimulating factor; protein binding; protein interaction; kinetics; ligands; receptor affinity; ligand binding; receptor binding; granulocyte-macrophage colony-stimulating factor; hl-60 cells; granulocyte macrophage colony stimulating factor receptor; receptors, granulocyte-macrophage colony-stimulating factor; receptor subunit; humans; human; priority journal; article |
| Journal Title: | Blood |
| Volume: | 94 |
| Issue: | 11 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1999-12-01 |
| Start Page: | 3748 |
| End Page: | 3753 |
| Language: | English |
| PUBMED: | 10572088 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V94.11.3748 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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