ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation

Autor: Anders M. Hinsby, Susan O. Meakin, Lone Juhl, Line Lundfald, Dorte Kornerup Ditlevsen, Vladimir Berezin, Elisabeth Bock, Irina Korshunova
Rok vydání: 2004
Předmět:
Src Homology 2 Domain-Containing
Transforming Protein 1
Neurite
Fibroblast Growth Factor Receptor Substrate 2
Biology
Proto-Oncogene Proteins c-fyn
Fibroblast growth factor
PC12 Cells
Biochemistry
Cell Line
Mice
Cellular and Molecular Neuroscience
FYN
Growth factor receptor
Proto-Oncogene Proteins
Neurites
Animals
Humans
Phosphorylation
Neural Cell Adhesion Molecules
Cells
Cultured
Adaptor Proteins
Signal Transducing
GRB2 Adaptor Protein
Neurons
Membrane Proteins
Phosphoproteins
Receptors
Fibroblast Growth Factor
Coculture Techniques
Rats
Cell biology
src-Family Kinases
Shc Signaling Adaptor Proteins
nervous system
Fibroblast growth factor receptor
embryonic structures
Fibroblast Growth Factor 2
Neural cell adhesion molecule
biological phenomena
cell phenomena
and immunity
Signal transduction
Zdroj: Journal of Neurochemistry. 91:694-703
ISSN: 1471-4159
0022-3042
DOI: 10.1111/j.1471-4159.2004.02772.x
Popis: Homophilic binding in trans of the neural cell adhesion molecule (NCAM) mediates adhesion between cells and leads, via activation of intracellular signaling cascades, to neurite outgrowth in primary neurons as well as in the neuronal cell line PC12. NCAM mediates neurite extension in PC12 cells by two principal routes of signaling: NCAM/Fyn and NCAM/fibroblast growth factor receptor (FGFR), respectively. Previous studies have shown that activation of mitogen-activated protein kinases is a pivotal point of convergence in NCAM signaling, but the mechanisms behind this activation are not clear. Here, we investigated the involvement of adaptor proteins in NCAM and fibroblast growth factor 2 (FGF2)-mediated neurite outgrowth in the PC12-E2 cell line. We found that both FGFR substrate-2 and Grb2 play important roles in NCAM as well as in FGF2-stimulated events. In contrast, the docking protein ShcA was pivotal to neurite outgrowth induced by NCAM, but not by FGF2, in PC12 cells. Moreover, in rat cerebellar granule neurons, phosphorylation of ShcA was stimulated by an NCAM mimicking peptide, but not by FGF2. This activation was blocked by inhibitors of both FGFR and Fyn, indicating that NCAM activates FGFR signaling in a manner distinct from FGF2 stimulation, and regulates ShcA phosphorylation by the concerted efforts of the NCAM/FGFR as well as the NCAM/Fyn signaling pathway.
Databáze: OpenAIRE
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