Glial Cell Line-Derived Neurotrophic Factor (GDNF) Receptor α-1 (GFRα1) Is Highly Selective for GDNF versus Artemin
| Autor: | Olivia Orozco, Paul Carmillo, Dane S. Worley, Carolyn Buckley, Lee Walus, Richard L. Cate, Carl Rosenblad, Anthony Rossomando, Lone Dagø, Dinah W. Y. Sah, Miller Stephan S, Albert Tse, Eric S. Day, Mette Grønborg, Adrian Whitty |
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| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Glial Cell Line-Derived Neurotrophic Factor Receptors Cell Survival animal diseases Artemin Nerve Tissue Proteins Transfection Biochemistry Cell Line Rats Sprague-Dawley Mice Neurotrophic factors Cell Line Tumor Ganglia Spinal Proto-Oncogene Proteins Glial cell line-derived neurotrophic factor Animals Humans Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Neurons Afferent Phosphorylation Receptor Protein kinase B biology urogenital system Cell Membrane Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Surface Plasmon Resonance Rats Cell biology Solutions nervous system biology.protein GDNF family of ligands Protein Binding Signal Transduction |
| Zdroj: | Biochemistry. 44:2545-2554 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | To clarify whether glial cell line-derived neurotrophic factor (GDNF) receptor alpha-1 (GFRalpha1), the glycosylphosphatidylinositol (GPI)-linked coreceptor for GDNF, is also a functional coreceptor for artemin (ART), we have studied receptor binding, signaling, and neuronal survival. In cell-free binding studies, GFRalpha1-Ig displayed strong preferential binding to GDNF, though in the presence of soluble RET, weak binding to ART could also be detected. However, using GFRalpha1-transfected NB41A3 cells, ART showed no detectable competition against the binding of (125)I-labeled GDNF. Moreover, ART failed to induce phosphorylation of extracellular signal-related kinase (ERK) and Akt in these cells and was10(4)-fold less potent than GDNF in stimulating RET phosphorylation. When rat primary dorsal root ganglion (DRG) neurons were used, only the survival promoting activity of GDNF and not that of ART was blocked by an anti-GFRalpha1 antibody. These results indicate that although ART can interact weakly with soluble GFRalpha1 constructs under certain circumstances in vitro, in cell-based functional assays GFRalpha1 is at least 10 000-fold selective for GDNF over ART. The extremely high selectivity of GFRalpha1 for GDNF over ART and the low reactivity of ART for this receptor suggest that GFRalpha1 is not likely to be a functional coreceptor for ART in vivo. |
| Databáze: | OpenAIRE |
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