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PMID: 8855235 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 20 ·1996-10-01 ·Pages 10657-61

Vega QC, Worby CA, Lechner MS, Dixon JE, Dressler GR

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.

MeSH Terms
Animals Drosophila Proteins Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Kidney/embryology Mice Morphogenesis Nerve Growth Factors Nerve Tissue Proteins/physiology Organ Culture Techniques Phosphotyrosine/metabolism Protein Binding Proto-Oncogene Proteins/physiology Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases/physiology Signal Transduction Ureter/embryology
Chemicals
Drosophila Proteins Gdnf protein, mouse Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Nerve Growth Factors Nerve Tissue Proteins Proto-Oncogene Proteins Phosphotyrosine Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Ret protein, Drosophila Ret protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Vega Q C
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109, USA.
Worby C A
Lechner M S
Dixon J E
Dressler G R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.20.10657
Published
1996-10-01
Pages
10657-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38210
Subset
IM
Grants
PHS HHS · 18849 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.20.10657 PMC Full Text View journal details
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