Abstract
Disabled 1 (Dab1) is an adapter protein for very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) and an integral component of the Reelin pathway which orchestrates neuronal layering during embryonic brain development. Activation of Dab1 is induced by binding of Reelin to ApoER2 and VLDLR and phosphorylation of Dab1 mediated by Src family kinases. Here we show that Dab1 also acts as an adaptor for epidermal growth factor receptor (EGFR) and can be phosphorylated by epidermal growth factor (EGF) binding to EGFR. Phosphorylation of Dab1 depends on the kinase activity of EGFR constituting a signal pathway independent of Reelin and its receptors.
Keywords:
Dab1; EGF; EGFR; cell proliferation; intestinal cells.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Proliferation
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Culture Media, Conditioned / metabolism
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Embryo, Mammalian
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Epidermal Growth Factor / metabolism
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Epithelial Cells / metabolism*
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ErbB Receptors / metabolism*
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Extracellular Matrix Proteins / metabolism
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Female
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HEK293 Cells
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Humans
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Intestinal Mucosa / cytology
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Male
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Mice
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NIH 3T3 Cells
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons
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Phosphorylation
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Primary Cell Culture
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Reelin Protein
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Serine Endopeptidases / metabolism
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Signal Transduction
Substances
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Adaptor Proteins, Signal Transducing
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Cell Adhesion Molecules, Neuronal
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Culture Media, Conditioned
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DAB1 protein, human
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Dab1 protein, mouse
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Extracellular Matrix Proteins
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Nerve Tissue Proteins
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Reelin Protein
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Epidermal Growth Factor
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EGFR protein, human
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EGFR protein, mouse
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ErbB Receptors
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RELN protein, human
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Reln protein, mouse
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Serine Endopeptidases