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Interaction of granulocyte colony-stimulating factor (G-CSF) with its receptor. Evidence that Glu19 of G-CSF interacts with Arg288 of the receptor.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 1999 Jun 18; Vol. 274 (25), pp. 17445-51. - Publication Year :
- 1999
-
Abstract
- Granulocyte colony-stimulating factor (G-CSF) forms a tetrameric complex with its receptor, comprising two G-CSF and two receptor molecules. The structure of the complex is unknown, and it is unclear whether there are one or two binding sites on G-CSF and the receptor. The immunoglobulin-like domain and the cytokine receptor homologous module of the receptor are involved in G-CSF binding, and Arg288 in the cytokine receptor homologous module is particularly important. To identify residues in G-CSF that interact with Arg288, selected charged residues in G-CSF were mutated to Ala. To clarify whether there are two binding sites, a chimeric receptor was created in which the Ig domain was replaced with that of the related receptor gp130. This chimera bound G-CSF but could not transduce a signal, consistent with failure of dimerization and loss of one binding site. The G-CSF mutants had reduced mitogenic activity on cells expressing wild-type receptor. When tested with the chimeric receptor, all G-CSF mutants except one (E46A) showed reduced binding, suggesting that Glu46 is important for interaction with the Ig domain. On cells expressing R288A receptor, all the G-CSF mutants except E19A showed reduced mitogenic activity, indicating that Glu19 of G-CSF interacts with Arg288 of the receptor.
- Subjects :
- Antigens, CD genetics
Binding Sites
Cell Division
Cell Line
Cytokine Receptor gp130
Dimerization
Flow Cytometry
Granulocyte Colony-Stimulating Factor genetics
Humans
Membrane Glycoproteins genetics
Mutation
Protein Binding
Receptors, Granulocyte Colony-Stimulating Factor genetics
Recombinant Fusion Proteins genetics
Arginine chemistry
Glutamic Acid chemistry
Granulocyte Colony-Stimulating Factor chemistry
Receptors, Granulocyte Colony-Stimulating Factor chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 274
- Issue :
- 25
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 10364174
- Full Text :
- https://doi.org/10.1074/jbc.274.25.17445