GDNF–Induced Activation of the Ret Protein Tyrosine Kinase Is Mediated by GDNFR-α, a Novel Receptor for GDNF

Autor: Jean-Claude Louis, Duanzhi Wen, Gary M. Fox, Zheng Hu, Rod Cupples, Paige Holst, Sylvia Hu, Laarni Antonio, Mei Fang, Shuqian Jing, Rami Tamir, Yanbin Yu, Yi Luo, Bruce W. Altrock
Jazyk: angličtina
Předmět:
endocrine system
Glial Cell Line-Derived Neurotrophic Factor Receptors
endocrine system diseases
Glycosylphosphatidylinositols
Neurturin
animal diseases
Persephin
Molecular Sequence Data
Artemin
Nerve Tissue Proteins
Receptors
Nerve Growth Factor
General Biochemistry
Genetics and Molecular Biology
Retina
Rats
Sprague-Dawley
Mice
Fetus
Neurotrophic factors
Proto-Oncogene Proteins
Glial cell line-derived neurotrophic factor
Animals
Drosophila Proteins
Amino Acid Sequence
Glial Cell Line-Derived Neurotrophic Factor
Nerve Growth Factors
Cloning
Molecular
Phosphorylation
Cells
Cultured
Motor Neurons
biology
Base Sequence
Dose-Response Relationship
Drug
Biochemistry
Genetics and Molecular Biology(all)
urogenital system
Proto-Oncogene Proteins c-ret
Membrane Proteins
Receptor Protein-Tyrosine Kinases
Molecular biology
Recombinant Proteins
Rats
Mice
Inbred C57BL
Spinal Cord
nervous system
biology.protein
Tyrosine
GDNF family of ligands
Tyrosine kinase
Zdroj: Cell. (7):1113-1124
ISSN: 0092-8674
DOI: 10.1016/S0092-8674(00)81311-2
Popis: We report the expression cloning and characterization of GDNFR-alpha, a novel glycosylphosphatidylinositol-linked cell surface receptor for glial cell line-derived neurotrophic factor (GDNF). GDNFR-alpha binds GDNF specifically and mediates activation of the Ret protein-tyrosine kinase (PTK). Treatment of Neuro-2a cells expressing GDNFR-alpha with GDNF rapidly stimulates Ret autophosphorylation. Ret is also activated by treatment with a combination of GDNF and soluble GDNFR-alpha in cells lacking GDNFR-alpha, and this effect is blocked by a soluble Ret-Fc fusion protein. Ret activation by GDNF was also observed in cultured embryonic rat spinal cord motor neurons, a cell type that responds to GDNF in vivo. A model for the stepwise formation of a GDNF signal-transducing complex including GDNF, GDNFR-alpha, and the Ret PTK is proposed.
Databáze: OpenAIRE
Externí odkaz: