| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 10, 8771-8779, March 7, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Molecular Genetics, Biochemistry, and
Microbiology, University of Cincinnati, College of Medicine,
Cincinnati, Ohio 45267-0524
JAGGED1 is a member of the Delta/Serrate/Lag-2
(DSL) family of proteins that are cell-bound ligands for Notch
receptors. Initiation of Notch signaling occurs through a series of
proteolytic events upon the binding of Notch to a DSL protein presented
on neighboring cells. Whether DSL proteins themselves are capable of
initiating an intrinsic signaling mechanism within the cell they are
expressed is not known. Aberrant misexpression of JAGGED1 and DELTA1
has been documented in several human tumors; however, the mechanism by
which misexpression of JAGGED1 contributes to oncogenesis has not been
elucidated. We report that expression of human JAGGED1 transforms RKE
cells in culture, therefore providing a model system to elucidate the
function of DSL proteins. JAGGED1-mediated transformation occurs in a
dose-dependent manner and requires a PDZ-ligand at the C
terminus. Mutation of the PDZ-ligand did not affect the ability of
JAGGED1 to initiate Notch signaling in neighboring cells. However, the
PDZ-ligand is required for changes in the expression of JAGGED1 target
genes and transcriptional activation of luciferase reporter constructs.
Our data indicate the existence of a novel PDZ-dependent
signaling pathway intrinsic to JAGGED1. We propose a bi-directional
signaling model such that DSL proteins may have two distinct functions:
to initiate Notch signaling in a neighboring cell and to initiate a
PDZ-dependent signaling mechanism in the DSL-expressing
cell. Moreover, we conclude that this intrinsic signaling
mechanism of JAGGED1 may partly provide a link between aberrant
misexpression of JAGGED1 and tumorigenesis.
The C-terminal PDZ-Ligand of JAGGED1 Is Essential
for Cellular Transformation*,
*
This work was funded in part by Grant RPG LBC-99465 from the
American Cancer Society (to A. J. C.) and Grant ROI CA 83736 from the
National Cancer Institute (to A. J. C.) and the NCI National Institutes of Health Training Grant 5T32 CA59268 (to J. M. A.). A. J. C. is a scholar of the Leukemia and Lymphoma Society (Award 1298-02).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The on-line version of this article (available at
http://www.jbc.org) contains supplementary data.
To whom correspondence should be addressed: 231 Albert Sabin Way,
Dept. of Molecular Genetics, University of Cincinnati, College of
Medicine, Cincinnati, OH 45267-0524. Tel.: 513-558-3664; Fax: 513-558-8474; E-mail: tony.capobianco@uc.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Urs, A. Roudabush, C. F. O'Neill, I. Pinz, I. Prudovsky, D. Kacer, Y. Tang, L. Liaw, and D. Small Soluble Forms of the Notch Ligands Delta1 and Jagged1 Promote in Vivo Tumorigenicity in NIH3T3 Fibroblasts with Distinct Phenotypes Am. J. Pathol., September 1, 2008; 173(3): 865 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Choi, J. T. Park, B. Davidson, P. J. Morin, I.-M. Shih, and T.-L. Wang Jagged-1 and Notch3 Juxtacrine Loop Regulates Ovarian Tumor Growth and Adhesion Cancer Res., July 15, 2008; 68(14): 5716 - 5723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Holderfield and C. C.W. Hughes Crosstalk Between Vascular Endothelial Growth Factor, Notch, and Transforming Growth Factor-{beta} in Vascular Morphogenesis Circ. Res., March 28, 2008; 102(6): 637 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Estrach, J. Legg, and F. M. Watt Syntenin mediates Delta1-induced cohesiveness of epidermal stem cells in culture J. Cell Sci., August 15, 2007; 120(16): 2944 - 2952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Geffers, K. Serth, G. Chapman, R. Jaekel, K. Schuster-Gossler, R. Cordes, D. B. Sparrow, E. Kremmer, S. L. Dunwoodie, T. Klein, et al. Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo J. Cell Biol., July 24, 2007; 178(3): 465 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Niessen and A. Karsan Notch signaling in the developing cardiovascular system Am J Physiol Cell Physiol, July 1, 2007; 293(1): C1 - C11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Taelman, C. Van Campenhout, M. Solter, T. Pieler, and E. J. Bellefroid The Notch-effector HRT1 gene plays a role in glomerular development and patterning of the Xenopus pronephros anlagen Development, August 1, 2006; 133(15): 2961 - 2971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Reedijk, S. Odorcic, L. Chang, H. Zhang, N. Miller, D. R. McCready, G. Lockwood, and S. E. Egan High-level Coexpression of JAG1 and NOTCH1 Is Observed in Human Breast Cancer and Is Associated with Poor Overall Survival Cancer Res., September 15, 2005; 65(18): 8530 - 8537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ladi, J. T. Nichols, W. Ge, A. Miyamoto, C. Yao, L.-T. Yang, J. Boulter, Y. E. Sun, C. Kintner, and G. Weinmaster The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands J. Cell Biol., September 12, 2005; 170(6): 983 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mizuhara, T. Nakatani, Y. Minaki, Y. Sakamoto, Y. Ono, and Y. Takai MAGI1 Recruits Dll1 to Cadherin-based Adherens Junctions and Stabilizes It on the Cell Surface J. Biol. Chem., July 15, 2005; 280(28): 26499 - 26507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Veeraraghavalu, V. K. Subbaiah, S. Srivastava, O. Chakrabarti, R. Syal, and S. Krishna Complementation of Human Papillomavirus Type 16 E6 and E7 by Jagged1-Specific Notch1-Phosphatidylinositol 3-Kinase Signaling Involves Pleiotropic Oncogenic Functions Independent of CBF1;Su(H);Lag-1 Activation J. Virol., June 15, 2005; 79(12): 7889 - 7898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Purow, R. M. Haque, M. W. Noel, Q. Su, M. J. Burdick, J. Lee, T. Sundaresan, S. Pastorino, J. K. Park, I. Mikolaenko, et al. Expression of Notch-1 and Its Ligands, Delta-Like-1 and Jagged-1, Is Critical for Glioma Cell Survival and Proliferation Cancer Res., March 15, 2005; 65(6): 2353 - 2363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Six, D. Ndiaye, G. Sauer, Y. Laabi, R. Athman, A. Cumano, C. Brou, A. Israel, and F. Logeat The Notch Ligand Delta1 Recruits Dlg1 at Cell-Cell Contacts and Regulates Cell Migration J. Biol. Chem., December 31, 2004; 279(53): 55818 - 55826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Santagata, F. Demichelis, A. Riva, S. Varambally, M. D. Hofer, J. L. Kutok, R. Kim, J. Tang, J. E. Montie, A. M. Chinnaiyan, et al. JAGGED1 Expression Is Associated with Prostate Cancer Metastasis and Recurrence Cancer Res., October 1, 2004; 64(19): 6854 - 6857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Veeraraghavalu, M. Pett, R. V. Kumar, P. Nair, A. Rangarajan, M. A. Stanley, and S. Krishna Papillomavirus-Mediated Neoplastic Progression Is Associated with Reciprocal Changes in Jagged1 and Manic Fringe Expression Linked to Notch Activation J. Virol., August 15, 2004; 78(16): 8687 - 8700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Trifonova, D. Small, D. Kacer, D. Kovalenko, V. Kolev, A. Mandinova, R. Soldi, L. Liaw, I. Prudovsky, and T. Maciag The non-transmembrane form of Delta1 but not of jagged1 Induces normal migratory behavior accompanied by FGF receptor 1-dependent transformation J. Biol. Chem., February 9, 2004; (2004) 300564200. [Abstract] [PDF]
|
|
|
|
|
|
M. J. LaVoie and D. J. Selkoe The Notch Ligands, Jagged and Delta, Are Sequentially Processed by {alpha}-Secretase and Presenilin/{gamma}-Secretase and Release Signaling Fragments J. Biol. Chem., September 5, 2003; 278(36): 34427 - 34437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Six, D. Ndiaye, Y. Laabi, C. Brou, N. Gupta-Rossi, A. Israel, and F. Logeat The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and {gamma}-secretase PNAS, June 24, 2003; 100(13): 7638 - 7643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Bland, P. Kimberly, and M. D. Rand Notch-induced Proteolysis and Nuclear Localization of the Delta Ligand J. Biol. Chem., April 11, 2003; 278(16): 13607 - 13610. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
