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GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF.

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.

Pubmed ID: 8674117

Authors

  • Jing S
  • Wen D
  • Yu Y
  • Holst PL
  • Luo Y
  • Fang M
  • Tamir R
  • Antonio L
  • Hu Z
  • Cupples R
  • Louis JC
  • Hu S
  • Altrock BW
  • Fox GM

Journal

Cell

Publication Data

June 28, 1996

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Cloning, Molecular
  • Dose-Response Relationship, Drug
  • Drosophila Proteins
  • Fetus
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Motor Neurons
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Phosphorylation
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Nerve Growth Factor
  • Recombinant Proteins
  • Retina
  • Spinal Cord
  • Tyrosine