GFRα-2 and GFRα-3 are two new receptors for ligands of the GDNF family

Shuqian Jing, Yanbin Yu, Mei Fang, Zheng Hu, Paige L. Holst, Thomas Boone, John Delaney, Henry Schultz, Renping Zhou, Gary M. Fox

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Abstract

The receptor for glial cell line-derived neurotrophic factor (GDNF) consists of GFRα-1 and Ret. Neurturin is a GDNF-related neurotrophin whose receptor is presently unknown. Here we report that neurturin can bind to either GFRα-1 or GFRα-2, a novel receptor related to GFRα-1. Both GFRα-1 and GFRα-2 mediate neurturin-induced Ret phosphorylation. GDNF can also bind to either GFRα-1 or GFRα-2, and activate Ret in the presence of either binding receptor. Although both ligands interact with both receptors, cells expressing GFRα-1 bind GDNF more efficiently than neurturin, while cells expressing GFRα-2 bind neurturin preferentially. Cross-linking and Ret activation data also suggest that while there is cross-talk, GFRα-1 is the primary receptor for GDNF and GFRα-2 exhibits a preference for neurturin. We have also cloned a cDNA that apparently codes for a third member of the GFRα receptor family. This putative receptor, designated GFRα-3, is closely related in amine acid sequence and is nearly identical in the spacing of its cysteine residues to both GFRα-1 and GFRα-2. Analysis of the tissue distribution of GFRα-1, GFRα-2, GFRα-3, and Ret by Northern blot reveals overlapping but distinct patterns of expression. Consistent with a role in GDNF function, the GFRαs and Ret are expressed in many of the same tissues, suggesting that GFRαs mediate the action of GDNF family ligands in vivo.

Original languageEnglish (US)
Pages (from-to)33111-33117
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number52
DOIs
StatePublished - Dec 26 1997

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Jing, S., Yu, Y., Fang, M., Hu, Z., Holst, P. L., Boone, T., Delaney, J., Schultz, H., Zhou, R., & Fox, G. M. (1997). GFRα-2 and GFRα-3 are two new receptors for ligands of the GDNF family. Journal of Biological Chemistry, 272(52), 33111-33117. https://doi.org/10.1074/jbc.272.52.33111