The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Ret-dependent and -independent Mechanisms of Glial Cell Line-derived Neurotrophic Factor Signaling in Neuronal Cells
Open accessAbstract
Glial cell line-derived neurotrophic factor (GDNF) has been shown to signal through a multicomponent receptor complex consisting of the Ret receptor tyrosine kinase and a member of the GFRalpha family of glycosylphosphatidylinositol-anchored receptors. In the current model of GDNF signaling, Ret delivers the intracellular signal but cannot bind ligand on its own, while GFRalphas bind ligand but are thought not to signal in the absence of Ret. We have compared signaling pathways activated by GDNF in two neuronal cell lines expressing different complements of GDNF receptors. In a motorneuron-derived cell line expressing Ret and GFRalphas, GDNF stimulated sustained activation of the Ras/ERK and phosphatidylinositol 3-kinase/Akt pathways, cAMP response element-binding protein phosphorylation, and increased c-fos expression. Unexpectedly, GDNF also promoted biochemical and biological responses in a line of conditionally immortalized neuronal precursors that express high levels of GFRalphas but not Ret. GDNF treatment did not activate the Ras/ERK pathway in these cells, but stimulated a GFRalpha1-associated Src-like kinase activity in detergent-insoluble membrane compartments, rapid phosphorylation of cAMP response element-binding protein, up-regulation of c-fos mRNA, and cell survival. Together, these results offer new insights into the dynamics of GDNF signaling in neuronal cells, and indicate the existence of novel signaling mechanisms directly or indirectly mediated by GFRalpha receptors acting in a cell-autonomous manner independently of Ret.
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Cites
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Cited by
Lipid rafts and signal transduction
Simons, K., & Toomre, D. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036052 · Cited by 5,371
Novel functions and signalling pathways for GDNF
Sariola, H., & Saarma, M. (2003) · Journal of Cell Science · doi:10.1242/jcs.00786 · Cited by 648
The Neural Cell Adhesion Molecule NCAM Is an Alternative Signaling Receptor for GDNF Family Ligands
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Self-citationRET tyrosine kinase signaling in development and cancer
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Santuccione, A., Sytnyk, V., Leshchyns'ka, I., & Schachner, M. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200409127 · Cited by 419
Metadata
- Authors
- Trupp, M., Scott, R., Whittemore, S. R., & Ibáñez, C. F.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-07
- Volume
- 274
- Issue
- 30
- Pages
- 20885-20894
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2110682302
- Cited by
- 318
- References
- 52
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Trupp, M., Scott, R., Whittemore, S. R., & Ibáñez, C. F. (1999). Ret-dependent and -independent Mechanisms of Glial Cell Line-derived Neurotrophic Factor Signaling in Neuronal Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.30.20885
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