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

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

Research output: Contribution to journalArticleResearchpeer-review

193 Citations (Scopus)

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

Fingerprint

Proto-Oncogene Proteins c-ret
Glial Cell Line-Derived Neurotrophic Factor Receptors
Glial Cell Line-Derived Neurotrophic Factor
Morphogenesis
Kidney
Enteric Nervous System
Organ Culture Techniques
Neutralizing Antibodies
Tyrosine
Anti-Idiotypic Antibodies
Catalytic Domain
Phosphorylation
Ligands

Keywords

  • kidney development
  • neurotrophin

Cite this

@article{b7f5890c2eed4910bf9ce217ff2884d2,
title = "Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis",
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.",
keywords = "kidney development, neurotrophin",
author = "Quinn Vega and Worby, {Carolyn A.} and Lechner, {Mark S.} and Dixon, {Jack E.} and Dressler, {Gregory R.}",
year = "1996",
month = "10",
day = "1",
doi = "10.1073/pnas.93.20.10657",
language = "English",
volume = "93",
pages = "10657--10661",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "20",

}

Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis. / Vega, Quinn; Worby, Carolyn A.; Lechner, Mark S.; Dixon, Jack E.; Dressler, Gregory R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 20, 01.10.1996, p. 10657-10661.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis

AU - Vega, Quinn

AU - Worby, Carolyn A.

AU - Lechner, Mark S.

AU - Dixon, Jack E.

AU - Dressler, Gregory R.

PY - 1996/10/1

Y1 - 1996/10/1

N2 - 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.

AB - 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.

KW - kidney development

KW - neurotrophin

UR - http://www.scopus.com/inward/record.url?scp=0029748327&partnerID=8YFLogxK

U2 - 10.1073/pnas.93.20.10657

DO - 10.1073/pnas.93.20.10657

M3 - Article

VL - 93

SP - 10657

EP - 10661

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 20

ER -