Activation of EGF Receptor Kinase by L1-mediated Homophilic Cell Interactions
| Autor: | Lars V. Kristiansen, Susana Romani, Rafique Islam, Luis Garcia-Alonso, Michael Hortsch |
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| Přispěvatelé: | Ministerio de Ciencia y Tecnología (España), European Commission, National Institute of Child Health and Human Development (US), National Science Foundation (US) |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Axonal fasciculation
Cell signaling animal structures Neurite Blotting Western Neural Cell Adhesion Molecule L1 Cell Communication Biology Transfection Models Biological Receptor tyrosine kinase Cell Line Cell Adhesion Animals Humans Phosphorylation Cell adhesion Molecular Biology Cell Biology Articles Precipitin Tests Cell biology Enzyme Activation ErbB Receptors Phenotype biology.protein Tyrosine Neural cell adhesion molecule Drosophila Electrophoresis Polyacrylamide Gel Signal transduction Tyrosine kinase Protein Binding Signal Transduction |
| ISSN: | 2001-1628 |
| Popis: | 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. This work was made possible in part by grants from Ministerio de Ciencia y Tecnologia (SAF2001-1628, in part FEDER) to L.G.-A. and the National Institute of Child Health and Human Development (RO1HD29388), the National Science Foundation (IBN-0132819), and the Spinal Cord Research Foundation (SCRF 1797) to M.H. |
| Databáze: | OpenAIRE |
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