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Distinct roles of EGF repeats for the Notch signaling system
- Source :
- Experimental cell research. 302(2)
- Publication Year :
- 2004
-
Abstract
- Notch is a single-pass transmembrane receptor that mediates cell fate choice in various species and developmental contexts. The Notch signal is transduced by its intracellular domain, which acts as a transcriptional activator, and is released from the plasma membrane by proteolytic cleavages. This process is initiated by intercellular association of the epidermal growth factor (EGF) repeats between Notch and the DSL (Delta, Serrate, Lag-2) ligands but the detailed mechanism is yet to be clarified. Here we demonstrate that Notch1 can form homodimers, which is achieved by its EGF motifs. The Notch1 dimer formation increased in response to ligand presentation and HES1 promoter was stimulated, implying that receptor homodimerization is an important initial step in Notch signal transduction. EGF motifs also serve as a protection against proteases, including TNF-alpha converting enzyme, which prevents Notch1 from ligand-independent activation. Multiple functions of the Notch EGF motifs, such as the prevention of constitutive activation, reciprocal interaction with the ligands and lateral interaction for homodimerization, appear to constitute crucial elements of the Notch signaling system.
- Subjects :
- EGF-like domain
Amino Acid Motifs
Notch signaling pathway
Chick Embryo
Biology
Cell fate determination
Ligands
Cell Line
Mice
Epidermal growth factor
Chlorocebus aethiops
Animals
Drosophila Proteins
Humans
HES1
Promoter Regions, Genetic
Repetitive Sequences, Nucleic Acid
Epidermal Growth Factor
Receptors, Notch
Cell Membrane
Membrane Proteins
Cell Biology
Transmembrane protein
Cell biology
Biochemistry
Notch proteins
COS Cells
NIH 3T3 Cells
Drosophila
Signal transduction
Dimerization
Signal Transduction
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 302
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....24ca0f4fb9ebf299919b76eb0a205479