spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
Development ePress online publication date 19 Nov 2003
doi: 10.1242/dev.00883

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.00883v1
130/26/6411    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lei, L.
Right arrow Articles by Irvine, K. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lei, L.
Right arrow Articles by Irvine, K. D.

Research article

An O-fucose site in the ligand binding domain inhibits Notch activation


Liang Lei, Aiguo Xu, Vladislav M. Panin, and Kenneth D. Irvine*
* Author for correspondence (e-mail: irvine{at}waksman.rutgers.edu)

Two glycosyltransferases that transfer sugars to EGF domains, OFUT1 and Fringe, regulate Notch signaling. However, sites of O-fucosylation on Notch that influence Notch activation have not been previously identified. Moreover, the influences of OFUT1 and Fringe on Notch activation can be positive or negative, depending on their levels of expression and on whether Delta or Serrate is signaling to Notch. Here, we describe the consequences of eliminating individual, highly conserved sites of O-fucose attachment to Notch. Our results indicate that glycosylation of an EGF domain proposed to be essential for ligand binding, EGF12, is crucial to the inhibition of Serrate-to-Notch signaling by Fringe. Expression of an EGF12 mutant of Notch (N-EGF12f) allows Notch activation by Serrate even in the presence of Fringe. By contrast, elimination of three other highly conserved sites of O-fucosylation does not have detectable effects. Binding assays with a soluble Notch extracellular domain fusion protein and ligand-expressing cells indicate that the N-EGF12f mutation can influence Notch activation by preventing Fringe from blocking Notch-Serrate binding. The N-EGF12f mutant can substitute for endogenous Notch during embryonic neurogenesis, but not at the dorsoventral boundary of the wing. Thus, inhibition of Notch-Serrate binding by O-fucosylation of EGF12 might be needed in certain contexts to allow efficient Notch signaling.


This article has been cited by other articles:


Home page
 J BiochemHome page
T. Okajima, A. Matsuura, and T. Matsuda
Biological Functions of Glycosyltransferase Genes Involved in O-fucose Glycan Synthesis
J. Biochem., July 1, 2008; 144(1): 1 - 6.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Stahl, K. Uemura, C. Ge, S. Shi, Y. Tashima, and P. Stanley
Roles of Pofut1 and O-Fucose in Mammalian Notch Signaling
J. Biol. Chem., May 16, 2008; 283(20): 13638 - 13651.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Cordle, C. RedfieldZ, M. Stacey, P. A. van der Merwe, A. C. Willis, B. R. Champion, S. Hambleton, and P. A. Handford
Localization of the Delta-like-1-binding Site in Human Notch-1 and Its Modulation by Calcium Affinity
J. Biol. Chem., April 25, 2008; 283(17): 11785 - 11793.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Ge and P. Stanley
The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development
PNAS, February 5, 2008; 105(5): 1539 - 1544.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. Raft, E. J. Koundakjian, H. Quinones, C. S. Jayasena, L. V. Goodrich, J. E. Johnson, N. Segil, and A. K. Groves
Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development
Development, December 15, 2007; 134(24): 4405 - 4415.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
U.-M. Fiuza and A. M. Arias
Cell and molecular biology of Notch
J. Endocrinol., September 1, 2007; 194(3): 459 - 474.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Shi, C. Ge, Y. Luo, X. Hou, R. S. Haltiwanger, and P. Stanley
The Threonine That Carries Fucose, but Not Fucose, Is Required for Cripto to Facilitate Nodal Signaling
J. Biol. Chem., July 13, 2007; 282(28): 20133 - 20141.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
N. Sasaki, T. Sasamura, H. O. Ishikawa, M. Kanai, R. Ueda, K. Saigo, and K. Matsuno
Polarized exocytosis and transcytosis of Notch during its apical localization in Drosophila epithelial cells.
Genes Cells, January 1, 2007; 12(1): 89 - 103.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Shi, M. Stahl, L. Lu, and P. Stanley
Canonical Notch Signaling Is Dispensable for Early Cell Fate Specifications in Mammals
Mol. Cell. Biol., November 1, 2005; 25(21): 9503 - 9508.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Rampal, J. F. Arboleda-Velasquez, A. Nita-Lazar, K. S. Kosik, and R. S. Haltiwanger
Highly Conserved O-Fucose Sites Have Distinct Effects on Notch1 Function
J. Biol. Chem., September 16, 2005; 280(37): 32133 - 32140.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Xu, L. Lei, and K. D. Irvine
Regions of Drosophila Notch That Contribute to Ligand Binding and the Modulatory Influence of Fringe
J. Biol. Chem., August 26, 2005; 280(34): 30158 - 30165.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
L.-T. Yang, J. T. Nichols, C. Yao, J. O. Manilay, E. A. Robey, and G. Weinmaster
Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1
Mol. Biol. Cell, February 1, 2005; 16(2): 927 - 942.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2003