Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-1-17
pubmed:abstractText
The neural cell adhesion molecule (NCAM) plays important roles in neuronal development, regeneration, and synaptic plasticity. NCAM homophilic binding mediates cell adhesion and induces intracellular signals, in which the fibroblast growth factor receptor plays a prominent role. Recent studies on axon guidance in Drosophila suggest that NCAM also regulates the epidermal growth factor receptor (EGFR) (Molecular and Cellular Neuroscience, 28, 2005, 141). A possible interaction between NCAM and EGFR in mammalian cells has not been investigated. The present study demonstrates for the first time a functional interaction between NCAM and EGFR in mammalian cells and investigates the molecular mechanisms underlying this interaction. First, NCAM and EGFR are shown to play opposite roles in neurite outgrowth regulation in cerebellar granular neurons. The data presented indicate that negative regulation of EGFR is one of the mechanisms underlying the neuritogenic effect of NCAM. Second, it is demonstrated that expression of the NCAM-180 isoform induces EGFR down-regulation in transfected cells and promotes EGFR down-regulation induced by EGF stimulation. It is demonstrated that the mechanism underlying this NCAM-180-induced EGFR down-regulation involves increased EGFR ubiquitination and lysosomal EGFR degradation. Furthermore, NCAM-180-mediated EGFR down-regulation requires NCAM homophilic binding and interactions of the cytoplasmic domain of NCAM-180 with intracellular interaction partners, but does not require NCAM-mediated fibroblast growth factor receptor activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
624-39
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17995934-Animals, pubmed-meshheading:17995934-Cell Adhesion, pubmed-meshheading:17995934-Cells, Cultured, pubmed-meshheading:17995934-Cerebellum, pubmed-meshheading:17995934-Coculture Techniques, pubmed-meshheading:17995934-Dose-Response Relationship, Drug, pubmed-meshheading:17995934-Down-Regulation, pubmed-meshheading:17995934-Drug Interactions, pubmed-meshheading:17995934-Enzyme Inhibitors, pubmed-meshheading:17995934-Humans, pubmed-meshheading:17995934-Mice, pubmed-meshheading:17995934-Molecular Weight, pubmed-meshheading:17995934-Neural Cell Adhesion Molecules, pubmed-meshheading:17995934-Neurites, pubmed-meshheading:17995934-Neurons, pubmed-meshheading:17995934-Protein Binding, pubmed-meshheading:17995934-Receptor, Epidermal Growth Factor, pubmed-meshheading:17995934-Receptors, Fibroblast Growth Factor, pubmed-meshheading:17995934-Transfection
pubmed:year
2008
pubmed:articleTitle
Neural cell adhesion molecule-180-mediated homophilic binding induces epidermal growth factor receptor (EGFR) down-regulation and uncouples the inhibitory function of EGFR in neurite outgrowth.
pubmed:affiliation
ENKAM Pharmaceuticals, Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't