HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 42, 41420-41430, October 17, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/42/41420    most recent M306425200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gross, I. Articles by Licht, J. D. Search for Related Content PubMed PubMed Citation Articles by Gross, I. Articles by Licht, J. D. Social Bookmarking                      What's this?

The Receptor Tyrosine Kinase Regulator Sprouty1 Is a Target of the Tumor Suppressor WT1 and Important for Kidney Development^*

Isabelle Gross   ¶, Debra J. Morrison  ¶, Deborah P. Hyink , Kylie Georgas ||, Milton A. English , Mathias Mericskay **, Seiyu Hosono , David Sassoon **, Patricia D. Wilson , Melissa Little ||  and Jonathan D. Licht  

From the Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, ^||Institute for Molecular Bioscience, University of Queensland, St. Lucia, 4072 Australia, and ^**Department of Molecular, Cellular and Developmental Biology, Mount Sinai School of Medicine, New York, New York 10029

WT1 encodes a transcription factor involved in kidney development and tumorigenesis. Using representational difference analysis, we identified a new set of WT1 targets, including a homologue of the Drosophila receptor tyrosine kinase regulator, sprouty. Sprouty1 was up-regulated in cell lines expressing wild-type but not mutant WT1. WT1 bound to the endogenous sprouty1 promoter in vivo and directly regulated sprouty1 through an early growth response gene-1 binding site. Expression of Sprouty1 and WT1 overlapped in the developing metanephric mesenchyme, and Sprouty1, like WT1, plays a key role in the early steps of glomerulus formation. Disruption of Sprouty1 expression in embryonic kidney explants by antisense oligonucleotides reduced condensation of the metanephric mesenchyme, leading to a decreased number of glomeruli. In addition, sprouty1 was expressed in the ureteric tree and antisense-treated ureteric trees had cystic lumens. Therefore, sprouty1 represents a physiologically relevant target gene of WT1 during kidney development.

Received for publication, June 17, 2003 , and in revised form, July 23, 2003.

^* This work was supported by National Institutes of Health Grant CA59998, the T. J. Martell Foundation for Cancer, AIDS, and Leukemia Research (to J. D. L.), the Association Pour La Recherche sur le Cancer (to I. G.), the American Foundation for Urologic Disease (to D. M.), and the National Health and Medical Research Council, Australia (to M. L.). Confocal microscopy performed at the Mount Sinai School of Medicine Microscopy Shared Resource Facility was supported by National Institutes of Health Grant CA95823. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: INSERM U381, Strasbourg, France.

^¶ These authors contributed equally to this work.

A Sylvia and Charles Viertel Senior Research Fellow.

To whom correspondence should be addressed: Box 1130, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029. Tel.: 212-659-5487; Fax: 212-849-2523; E-mail: jonathan.licht{at}mssm.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. J. Morrison, M. K.H. Kim, W. Berkofsky-Fessler, and J. D. Licht WT1 Induction of Mitogen-Activated Protein Kinase Phosphatase 3 Represents a Novel Mechanism of Growth Suppression Mol. Cancer Res., July 1, 2008; 6(7): 1225 - 1231. [Abstract] [Full Text] [PDF]

				F. Jaggi, M. A. Cabrita, A.-K. T. Perl, and G. Christofori Modulation of Endocrine Pancreas Development but not {beta}-Cell Carcinogenesis by Sprouty4 Mol. Cancer Res., March 1, 2008; 6(3): 468 - 482. [Abstract] [Full Text] [PDF]

				F. Edwin and T. B. Patel A Novel Role of Sprouty 2 in Regulating Cellular Apoptosis J. Biol. Chem., February 8, 2008; 283(6): 3181 - 3190. [Abstract] [Full Text] [PDF]

				H. Sutterluty, C.-E. Mayer, U. Setinek, J. Attems, S. Ovtcharov, M. Mikula, W. Mikulits, M. Micksche, and W. Berger Down-Regulation of Sprouty2 in Non-Small Cell Lung Cancer Contributes to Tumor Malignancy via Extracellular Signal-Regulated Kinase Pathway-Dependent and -Independent Mechanisms Mol. Cancer Res., May 1, 2007; 5(5): 509 - 520. [Abstract] [Full Text] [PDF]

				P. Hohenstein and N. D. Hastie The many facets of the Wilms' tumour gene, WT1 Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R196 - R201. [Abstract] [Full Text] [PDF]

				M. A. Cabrita, F. Jaggi, S. P. Widjaja, and G. Christofori A Functional Interaction between Sprouty Proteins and Caveolin-1 J. Biol. Chem., September 29, 2006; 281(39): 29201 - 2912. [Abstract] [Full Text] [PDF]

				G. Challen, B. Gardiner, G. Caruana, X. Kostoulias, G. Martinez, M. Crowe, D. F. Taylor, J. Bertram, M. Little, and S. M. Grimmond Temporal and spatial transcriptional programs in murine kidney development Physiol Genomics, October 17, 2005; 23(2): 159 - 171. [Abstract] [Full Text] [PDF]

				D. J. Morrison, M. A. English, and J. D. Licht WT1 Induces Apoptosis through Transcriptional Regulation of the Proapoptotic Bcl-2 Family Member Bak Cancer Res., September 15, 2005; 65(18): 8174 - 8182. [Abstract] [Full Text] [PDF]

				A. O. Perantoni, O. Timofeeva, F. Naillat, C. Richman, S. Pajni-Underwood, C. Wilson, S. Vainio, L. F. Dove, and M. Lewandoski Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development Development, September 1, 2005; 132(17): 3859 - 3871. [Abstract] [Full Text] [PDF]

				N. Trakul, R. E. Menard, G. R. Schade, Z. Qian, and M. R. Rosner Raf Kinase Inhibitory Protein Regulates Raf-1 but Not B-Raf Kinase Activation J. Biol. Chem., July 1, 2005; 280(26): 24931 - 24940. [Abstract] [Full Text] [PDF]

				C.-M. Li, C. E. Kim, A. A. Margolin, M. Guo, J. Zhu, J. M. Mason, T. W. Hensle, V. V.V.S. Murty, P. E. Grundy, E. R. Fearon, et al. CTNNB1 Mutations and Overexpression of Wnt/{beta}-Catenin Target Genes in WT1-Mutant Wilms' Tumors Am. J. Pathol., December 1, 2004; 165(6): 1943 - 1953. [Abstract] [Full Text] [PDF]

				T. L. Lo, P. Yusoff, C. W. Fong, K. Guo, B. J. McCaw, W. A. Phillips, H. Yang, E. S. M. Wong, H. F. Leong, Q. Zeng, et al. The Ras/Mitogen-Activated Protein Kinase Pathway Inhibitor and Likely Tumor Suppressor Proteins, Sprouty 1 and Sprouty 2 Are Deregulated in Breast Cancer Cancer Res., September 1, 2004; 64(17): 6127 - 6136. [Abstract] [Full Text] [PDF]

				L. Chi, S. Zhang, Y. Lin, R. Prunskaite-Hyyrylainen, R. Vuolteenaho, P. Itaranta, and S. Vainio Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development Development, July 15, 2004; 131(14): 3345 - 3356. [Abstract] [Full Text] [PDF]

				J. M. Mason, D. J. Morrison, B. Bassit, M. Dimri, H. Band, J. D. Licht, and I. Gross Tyrosine Phosphorylation of Sprouty Proteins Regulates Their Ability to Inhibit Growth Factor Signaling: A Dual Feedback Loop Mol. Biol. Cell, May 1, 2004; 15(5): 2176 - 2188. [Abstract] [Full Text] [PDF]

				M. T. Discenza and J. Pelletier Insights into the physiological role of WT1 from studies of genetically modified mice Physiol Genomics, February 13, 2004; 16(3): 287 - 300. [Abstract] [Full Text] [PDF]