The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Manilay, J. O.
Right arrow Articles by Robey, E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Manilay, J. O.
Right arrow Articles by Robey, E. A.
The Journal of Immunology, 2005, 174: 6732-6741.
Copyright © 2005 by The American Association of Immunologists

Impairment of Thymocyte Development by Dominant-Negative Kuzbanian (ADAM-10) Is Rescued by the Notch Ligand, Delta-11

Jennifer O. Manilay, Ana C. Anderson2, Chulho Kang and Ellen A. Robey3

Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

Although Notch plays a crucial role in T cell development, regulation of Notch signaling in the thymus is not well understood. Kuzbanian, an ADAM protease, has been implicated in the cleavage of both Notch receptors and the Notch ligand, Delta. In this study we show that the expression of a dominant-negative form of Kuzbanian (dnKuz) leads to reduced TCR{beta} expression in double-negative thymocytes and to a partial block between the double-negative to double-positive stages of development. These defects were rescued by overexpression of Delta-1 on thymocytes. Mixed chimeras showed a cell-autonomous block by dnKuz, but non-cell-autonomous rescue by Delta-1. This suggests that dnKuz impairs Notch signaling in receiving cells, and increasing Delta-1 on sending cells overcomes this defect. Interestingly, the expression of an activated form of Notch-1 rescued some, but not all, the defects in dnKuz Tg mice. Our data suggest that multiple Notch-dependent steps in early thymocyte development require Kuzbanian, but differ in the involvement of other Notch signaling components.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
G. van Tetering, P. van Diest, I. Verlaan, E. van der Wall, R. Kopan, and M. Vooijs
Metalloprotease ADAM10 Is Required for Notch1 Site 2 Cleavage
J. Biol. Chem., November 6, 2009; 284(45): 31018 - 31027.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. C. Bozkulak and G. Weinmaster
Selective Use of ADAM10 and ADAM17 in Activation of Notch1 Signaling
Mol. Cell. Biol., November 1, 2009; 29(21): 5679 - 5695.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
L. Tian, X. Wu, C. Chi, M. Han, T. Xu, and Y. Zhuang
ADAM10 is essential for proteolytic activation of Notch during thymocyte development
Int. Immunol., September 1, 2008; 20(9): 1181 - 1187.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Li, K. Boyd, P. J. Dempsey, and D. A. A. Vignali
Non-Cell Autonomous Expression of TNF-{alpha}-Converting Enzyme ADAM17 Is Required for Normal Lymphocyte Development
J. Immunol., April 1, 2007; 178(7): 4214 - 4221.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
G. Weinmaster and R. Kopan
A garden of Notch-ly delights
Development, September 1, 2006; 133(17): 3277 - 3282.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.