title: Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling.
abstract: Many cell-surface receptors transmit signals to the nucleus through complex protein cascades. By contrast, the Notch signalling pathway uses a relatively direct mechanism, in which the intracellular domain of the receptor is liberated by intramembrane cleavage and translocates to the nucleus. This critical cleavage is mediated by the gamma-secretase complex, and new findings reveal that this mechanism is used by various receptors, although many questions remain about the biochemical details.
authors.affiliation: Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 560, Room 22-12, Fort Detrick, Frederick, Maryland 21702, USA. fortini@ncifcrf.gov
authors.forename: Mark E
authors.initials: ME
authors.lastname: Fortini
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002462:Cell Membrane / Q000201:enzymology; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051880:Receptors, Notch; D015398:Signal Transduction
chemical_list: D046911:Macromolecular Substances; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human