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Processing of the Notch Ligand Delta by the Metalloprotease Kuzbanian
Abstract
Signaling by the Notch surface receptor controls cell fate determination in a broad spectrum of tissues. This signaling is triggered by the interaction of the Notch protein with what, so far, have been thought to be transmembrane ligands expressed on adjacent cells. Here biochemical and genetic analyses show that the ligand Delta is cleaved on the surface, releasing an extracellular fragment capable of binding to Notch and acting as an agonist of Notch activity. The ADAM disintegrin metalloprotease Kuzbanian is required for this processing event. These observations raise the possibility that Notch signaling in vivo is modulated by soluble forms of the Notch ligands.
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Citations
Cited by
Notch Signaling: Cell Fate Control and Signal Integration in Development
Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999) · Science · doi:10.1126/science.284.5415.770 · Cited by 5,909
Self-citationNotch signalling: a simple pathway becomes complex
Bray, S. J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2009 · Cited by 2,620
EDWARDS, D., HANDSLEY, M., & PENNINGTON, C. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.001 · Cited by 1,161
Lammich, S., Kojro, E., Postina, R., Gilbert, S., Pfeiffer, R., Jasionowski, M., Haass, C., & Fahrenholz, F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3922 · Cited by 975
Ligand endocytosis drives receptor dissociation and activation in the Notch pathway
Parks, A. L., Klueg, K. M., Stout, J. R., & Muskavitch, M. A. T. (2000) · Development · doi:10.1242/dev.127.7.1373 · Cited by 494
Metadata
- Authors
- Qi, H., D. Rand, M., Wu, X., Sestan, N., Wang, W., Rakic, P., Xu, T., & Artavanis-Tsakonas, S.
- Venue
- Science
- Published
- 1999-01
- Volume
- 283
- Issue
- 5398
- Pages
- 91-94
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1669956823
- Cited by
- 415
- References
- 0
- FWCI
- 18.16
- Type
- journal article
- Language
- en
- Open access
- closed
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- Qi, H., D. Rand, M., Wu, X., Sestan, N., Wang, W., Rakic, P., Xu, T., & Artavanis-Tsakonas, S. (1999). Processing of the Notch Ligand Delta by the Metalloprotease Kuzbanian. Science. https://doi.org/10.1126/science.283.5398.91
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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