XIB4035, a novel nonpeptidyl small molecule agonist for GFRα-1
Autor: | Kyoko Yamamoto, Masahiko Sakai, Kimiko Tokugawa, Shigeyuki Chaki, Tomokazu Ueki, Mariko Nishiguchi, Takumi Sekine, Shigeru Okuyama |
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Rok vydání: | 2003 |
Předmět: |
Receptor complex
Glial Cell Line-Derived Neurotrophic Factor Receptors Neurite Binding Competitive Antiparkinson Agents Mice Neuroblastoma Cellular and Molecular Neuroscience Neurotrophic factors Proto-Oncogene Proteins Neurites Tumor Cells Cultured Glial cell line-derived neurotrophic factor Animals Drosophila Proteins Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Phosphorylation Receptor Molecular Structure biology Chemistry Proto-Oncogene Proteins c-ret Autophosphorylation Receptor Protein-Tyrosine Kinases Cell Biology Neoplasm Proteins Cell biology nervous system Depression Chemical Quinolines biology.protein Protein Processing Post-Translational GDNF family of ligands Protein Binding Neurotrophin |
Zdroj: | Neurochemistry International. 42:81-86 |
ISSN: | 0197-0186 |
Popis: | We investigated the agonistic activities of N(4)-(7-chloro-2-[(E)-2-(2-chloro-phenyl)-vinyl]-quinolin-4-yl)-N(1),N(1)-diethyl-pentane-1,4-diamine (XIB4035), at the glial cell line-derived neurotrophic factor (GDNF) family receptoralpha-1(GFRalpha-1) in Neuro-2A cells, a mouse neuroblastoma cell line which is a suitable model for investigating functions mediated through GFRalpha-1. XIB4035 concentration-dependently inhibited [(125)I]GDNF binding in Neuro-2A cells with an IC(50) of 10.4 microM. GDNF induced autophosphorylation of Ret protein, and promoted neurite outgrowth in Neuro-2A cells. XIB4035, like GDNF, induced Ret autophosphorylation in the Neuro-2A cells. Moreover, XIB4035 promoted neurite outgrowth in a concentration-dependent manner. These results show that XIB4035 may act as an agonist at GFRalpha-1 receptor complex, and mimic neurotrophic effects of GDNF in Neuro-2A cells. This is an interesting finding showing that a nonpeptidyl small molecule is capable of inducing activation of a receptor that normally bind a relatively large protein ligand such as GDNF. |
Databáze: | OpenAIRE |
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