Glial Cell Line-derived Neurotrophic Factor Signals through the RET Receptor and Activates Mitogen-activated Protein Kinase

doi:10.1074/jbc.271.39.23619

Glial Cell Line-derived Neurotrophic Factor Signals through the RET Receptor and Activates Mitogen-activated Protein Kinase*

From the Department of Biological Chemistry, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0606

^∥To whom correspondence should be addressed:
Dept. of Biological Chemistry, University of Michigan Medical School, Rm. 5416 Medical Science I, Ann Arbor, MI 48109-0606.
Tel.: 313-764-8154; Fax: 313-763-4581.

Abstract

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β family of growth factors, was first identified by its ability to promote the survival of midbrain dopaminergic neurons in culture. We demonstrate that GDNF treatment of several neuroblastoma cell lines leads to dose-dependent tyrosine phosphorylation of the RET receptor and that other transforming growth factor-β family members are not able to activate the RET receptor. GDNF treatment of neuroblastoma cells also results in increased transcription of an Elk luciferase reporter gene, suggesting that GDNF activates the mitogen-activated protein kinase signal transduction pathway.

Footnotes

↵^† National Kidney Foundation Fellow.
↵^§ Recipient of a National Research Service Award postdoctoral fellowship from the NIDDK, National Institutes of Health.
↵^¶ Supported by the Deutsche Forschungsgemeinschaft.
↵* This work was supported by Grant 18849 from the NIDDK, National Institutes of Health (to J. E. D.) and a grant from the National Alliance for Research on Schizophrenia and Depression (to C. A. W.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

MEN

multiple endocrine neoplasia

GDNF

glial cell line-derived neurotrophic factor

TGF

transforming growth factor

MAPK

mitogen-activated protein kinase

CAT

chloramphenicol acetyltransferase

PAGE

polyacrylamide gel electrophoresis

PMA

12-O-tetradecanoyl phorbol-13-acetate

SAPK

stress-activated protein kinase
- Received July 8, 1996.
- Revision received August 7, 1996.