Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis

Quinn C. Vega, Carolyn A. Worby, Mark S. Lechner, Jack E. Dixon, Gregory R. Dressler

Research output: Contribution to journalArticle

196 Scopus citations

Abstract

The receptor tyrosine kinase RET functions during the development of the kidney and the enteric nervous system, yet no ligand has been identified to date. This report demonstrates that the glial cell line-derived neurotrophic factor (GDNF) activates RET, as measured by tyrosine phosphorylation of the intracellular catalytic domain. GDNF also binds RET with a dissociation constant of 8 nM, and 125I-labeled GDNF can be coimmunoprecipitated with anti-RET antibodies. In addition, exogenous GDNF stimulates both branching and proliferation of embryonic kidneys in organ culture, whereas neutralizing antibodies against GDNF inhibit branching morphogenesis. These data indicate that RET and GDNF are components of a common signaling pathway and point to a role for GDNF in kidney development.

Original languageEnglish
Pages (from-to)10657-10661
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number20
DOIs
StatePublished - 1 Oct 1996

Keywords

  • kidney development
  • neurotrophin

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