γ-Secretase-mediated proteolysis in cell-surface-receptor signalling View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-09-01

AUTHORS

Mark E. Fortini

ABSTRACT

Key PointsThe presenilin–γ-secretase complex mediates the intramembrane proteolysis of the Notch receptor and the amyloid precursor protein (APP). Several lines of evidence indicate that presenilin is likely to function as the catalytic core of the γ-secretase proteolytic activity. APP and Notch have alternate intramembrane cleavage sites that depend on γ-secretase activity. Intramembrane cleavage of γ-secretase substrates is preceded by ectodomain shedding that is mediated by extracellular cleavage events. Several new putative γ-secretase substrates have recently been identified, including the ErbB4 receptor tyrosine kinase, the CD44 cell-surface protein, E-cadherin, and the low-density lipoprotein-receptor-related protein (LRP). For APP, ErbB4, CD44 and LRP, intramembrane proteolysis apparently liberates a signalling fragment of the molecule, which is similar to the role of this cleavage event in the Notch pathway. A newly characterized type of intramembrane proteolysis generates secreted ligands that activate the epidermal growth factor receptor (EGFR). More... »

PAGES

673-684

References to SciGraph publications

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1038/nrm910

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    http://dx.doi.org/10.1038/nrm910

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12209127


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    50 schema:description Key PointsThe presenilin–γ-secretase complex mediates the intramembrane proteolysis of the Notch receptor and the amyloid precursor protein (APP). Several lines of evidence indicate that presenilin is likely to function as the catalytic core of the γ-secretase proteolytic activity. APP and Notch have alternate intramembrane cleavage sites that depend on γ-secretase activity. Intramembrane cleavage of γ-secretase substrates is preceded by ectodomain shedding that is mediated by extracellular cleavage events. Several new putative γ-secretase substrates have recently been identified, including the ErbB4 receptor tyrosine kinase, the CD44 cell-surface protein, E-cadherin, and the low-density lipoprotein-receptor-related protein (LRP). For APP, ErbB4, CD44 and LRP, intramembrane proteolysis apparently liberates a signalling fragment of the molecule, which is similar to the role of this cleavage event in the Notch pathway. A newly characterized type of intramembrane proteolysis generates secreted ligands that activate the epidermal growth factor receptor (EGFR).
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