title: Down-regulation of Delta by proteolytic processing.
abstract: Notch signaling regulates cell fate decisions during development through local cell interactions. Signaling is triggered by the interaction of the Notch receptor with its transmembrane ligands expressed on adjacent cells. Recent studies suggest that Delta is cleaved to release an extracellular fragment, DlEC, by a mechanism that involves the activity of the metalloprotease Kuzbanian; however, the functional significance of that cleavage remains controversial. Using independent functional assays in vitro and in vivo, we examined the biological activity of purified soluble Delta forms and conclude that Delta cleavage is an important down-regulating event in Notch signaling. The data support a model whereby Delta inactivation is essential for providing the critical ligand/receptor expression differential between neighboring cells in order to distinguish the signaling versus the receiving partner.
authors.affiliation: Department of Cell Biology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Ketu
authors.initials: K
authors.lastname: Mishra-Gorur
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Rand
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perez-Villamil
authors.forename: Spyros
authors.initials: S
authors.lastname: Artavanis-Tsakonas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D019483:Disintegrins / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins; D005123:Eye; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D019476:Insect Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000378:metabolism; D051880:Receptors, Notch; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D012995:Solubility; D014158:Transcription, Genetic / Q000502:physiology; D014921:Wings, Animal
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D019483:Disintegrins; D029721:Drosophila Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D008666:Metalloendopeptidases; D010446:Peptide Fragments; D051880:Receptors, Notch; D012097:Repressor Proteins; C084530:E(spl)mdelta-HLH protein, Drosophila; C497759:N protein, Drosophila; C064045:delta protein; C100953:KUZ protein, Drosophila