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Cited by 83Axon Guidance and Neuronal SignalingCell Adhesion Molecules ResearchDevelopmental Biology and Gene Regulation

Activation of EGF Receptor Kinase by L1-mediated Homophilic Cell Interactions

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Islam, Rafique, Kristiansen, Lars V., Romani, Susana, Garcia-Alonso, Luis, Hortsch, Michael·2004·Molecular Biology of the Cell
DOI 10.1091/mbc.e03-05-0333PMC PMC379294
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Abstract

Neural cell adhesion molecules (CAMs) are important players during neurogenesis and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of these developmental processes entail the activation of cellular signaling cascades. Pharmacological and genetic evidence indicates that the neurite outgrowth-promoting activity of L1-type CAMs is at least in part mediated by the stimulation of neuronal receptor tyrosine kinases (RTKs), especially FGF and EGF receptors. It has long been suspected that neural CAMs might physically interact with RTKs, but their activation by specific cell adhesion events has not been directly demonstrated. Here we report that gain-of-function conditions of the Drosophila L1-type CAM Neuroglian result in profound sensory axon pathfinding defects in the developing Drosophila wing. This phenotype can be suppressed by decreasing the normal gene dosage of the Drosophila EGF receptor gene. Furthermore, in Drosophila S2 cells, cell adhesion mediated by human L1-CAM results in the specific activation of human EGF tyrosine kinase at cell contact sites and EGF receptors engage in a physical interaction with L1-CAM molecules. Thus L1-type CAMs are able to promote the adhesion-dependent activation of EGF receptor signaling in vitro and in vivo.

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  • ksr and Neuroglian (Nrg) promote ERK signaling.

    “both of which promote ERK signaling (133–136)”

    From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [136]

    The Results report that Neuroglian functions through EGFR, and the Discussion links L1-type proteins to activation of the neuronal MAPK pathway. The paper does not establish that Neuroglian specifically promotes ERK signaling, and the passages found do not address ksr (searched: ksr, ERK, and MAPK). (LLM, conf=0.80)

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Cited by

Sorted by citations

Authors
Islam, R., Kristiansen, L. V., Romani, S., Garcia-Alonso, L., & Hortsch, M.
Affiliations
  • University of Michigan (US)
  • King's College London (GB)
  • Instituto de Neurociencias CSIC-UMH, Universidad Miguel Hernandez, San Juan de Alicante, 03550 Spain
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2004-04
Volume
15
Issue
4
Pages
2003-2012
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.e03-05-0333
PMC
PMC379294
OpenAlex
W2004741567
Cited by
83
References
1
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 3 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 1 · 2012: 5
FWCI
2.47
Type
journal article
Language
en
Open access
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Weizmann Institute of Science
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD029388, R01-HD29388)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
L1CAM, EGF receptor, receptor tyrosine kinase activation, homophilic adhesion, CD56, Neuroglian, neurite outgrowth, Drosophila wing development, receptor tyrosine kinase signaling
MeSH terms
Animals, Cell Adhesion, Cell Communication, Cell Line, Drosophila, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Humans, Models, Biological, Phenotype, Phosphorylation, Precipitin Tests, Protein Binding, Transfection, Tyrosine, Blotting, Western, Signal Transduction, Neural Cell Adhesion Molecule L1, ErbB Receptors

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