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
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Germani, A.
Right arrow Articles by Varin-Blank, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Germani, A.
Right arrow Articles by Varin-Blank, N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 1999, p. 3798-3807, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

hSiah2 Is a New Vav Binding Protein Which Inhibits Vav-Mediated Signaling Pathways

Antonia Germani,* Francisco Romero,dagger Martin Houlard, Jacques Camonis,Dagger Sylvie Gisselbrecht, Siegmund Fischer, and Nadine Varin-Blank

Institut Cochin de Génétique Moléculaire, U363 INSERM, Hôpital Cochin, Université Paris V, 75014 Paris, France

Received 3 September 1998/Returned for modification 27 October 1998/Accepted 25 January 1999

The hematopoietic proto-oncogene vav has been characterized as a Rac1-GDP/GTP exchanger protein which regulates cytoskeletal reorganization as well as signaling pathways leading to the activation of stress-activated protein kinases (SAPK/JNKs). Furthermore, vav overexpression enhances basal and T-cell receptor (TCR)-mediated stimulation of the nuclear factor of activated T cells (NFAT). We report here the interaction between Vav and hSiah2, a mammalian homolog of Drosophila Seven in absentia (Sina) that has been implicated in R7 photoreceptor cell formation during Drosophila eye development via the proteasome degradation pathway. Vav and hSiah2 interact in vitro and in vivo and colocalize in the cytoplasm of hematopoietic cells. The Src homology domain of Vav and the C-terminal region of hSiah2 are required for this interaction. We provide evidence for a negative regulation by hSiah2 of Vav-induced basal and TCR-mediated NFAT-dependent transcription. Overexpression of hSiah2 also inhibits the onco-Vav-induced JNK activation. Although the Vav-interacting domain is located in the C-terminal portion of hSiah2, the N-terminal region of hSiah2 is necessary for the inhibitory role that seems to be independent of the proteasome degradation.

* Corresponding author. Mailing address: Institut Cochin de Génétique Moléculaire, U363 INSERM, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75014 Paris, France. Phone: 33(1)40469332. Fax: 33(1)46339297. E-mail: germani{at}cochin.inserm.fr.

dagger Present address: Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, 41080 Seville, Spain.

Dagger Present address: Institut Curie, U248 INSERM, 75005 Paris, France.

Molecular and Cellular Biology, May 1999, p. 3798-3807, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Nakayama, K., Qi, J., Ronai, Z. (2009). The Ubiquitin Ligase Siah2 and the Hypoxia Response. Mol Cancer Res 7: 443-451 [Abstract] [Full Text]  
  • Santelli, E., Leone, M., Li, C., Fukushima, T., Preece, N. E., Olson, A. J., Ely, K. R., Reed, J. C., Pellecchia, M., Liddington, R. C., Matsuzawa, S.-i. (2005). Structural Analysis of Siah1-Siah-interacting Protein Interactions and Insights into the Assembly of an E3 Ligase Multiprotein Complex. J. Biol. Chem. 280: 34278-34287 [Abstract] [Full Text]  
  • Venables, J. P., Dalgliesh, C., Paronetto, M. P., Skitt, L., Thornton, J. K., Saunders, P. T., Sette, C., Jones, K. T., Elliott, D. J. (2004). SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome. Hum Mol Genet 13: 1525-1534 [Abstract] [Full Text]  
  • Frew, I. J., Hammond, V. E., Dickins, R. A., Quinn, J. M. W., Walkley, C. R., Sims, N. A., Schnall, R., Della, N. G., Holloway, A. J., Digby, M. R., Janes, P. W., Tarlinton, D. M., Purton, L. E., Gillespie, M. T., Bowtell, D. D. L. (2003). Generation and Analysis of Siah2 Mutant Mice. Mol. Cell. Biol. 23: 9150-9161 [Abstract] [Full Text]  
  • Miura-Shimura, Y., Duan, L., Rao, N. L., Reddi, A. L., Shimura, H., Rottapel, R., Druker, B. J., Tsygankov, A., Band, V., Band, H. (2003). Cbl-mediated Ubiquitinylation and Negative Regulation of Vav. J. Biol. Chem. 278: 38495-38504 [Abstract] [Full Text]  
  • House, C. M., Frew, I. J., Huang, H.-L., Wiche, G., Traficante, N., Nice, E., Catimel, B., Bowtell, D. D. L. (2003). A binding motif for Siah ubiquitin ligase. Proc. Natl. Acad. Sci. USA 100: 3101-3106 [Abstract] [Full Text]  
  • Matsuzawa, S.-i., Li, C., Ni, C.-Z., Takayama, S., Reed, J. C., Ely, K. R. (2003). Structural Analysis of Siah1 and Its Interactions with Siah-interacting Protein (SIP). J. Biol. Chem. 278: 1837-1840 [Abstract] [Full Text]  
  • Li, S., Xu, C., Carthew, R. W. (2002). Phyllopod Acts as an Adaptor Protein To Link the Sina Ubiquitin Ligase to the Substrate Protein Tramtrack. Mol. Cell. Biol. 22: 6854-6865 [Abstract] [Full Text]  
  • Schmidt, A., Hall, A. (2002). Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 16: 1587-1609 [Full Text]  
  • Dickins, R. A., Frew, I. J., House, C. M., O'Bryan, M. K., Holloway, A. J., Haviv, I., Traficante, N., de Kretser, D. M., Bowtell, D. D. L. (2002). The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice. Mol. Cell. Biol. 22: 2294-2303 [Abstract] [Full Text]  
  • Bassermann, F., Jahn, T., Miething, C., Seipel, P., Bai, R.-Y., Coutinho, S., Tybulewicz, V. L., Peschel, C., Duyster, J. (2002). Association of Bcr-Abl with the Proto-oncogene Vav Is Implicated in Activation of the Rac-1 Pathway. J. Biol. Chem. 277: 12437-12445 [Abstract] [Full Text]  
  • Zeng, L., Sachdev, P., Yan, L., Chan, J. L., Trenkle, T., McClelland, M., Welsh, J., Wang, L.-H. (2000). Vav3 Mediates Receptor Protein Tyrosine Kinase Signaling, Regulates GTPase Activity, Modulates Cell Morphology, and Induces Cell Transformation. Mol. Cell. Biol. 20: 9212-9224 [Abstract] [Full Text]  
  • Hehner, S. P., Hofmann, T. G., Dienz, O., Droge, W., Schmitz, M. L. (2000). Tyrosine-phosphorylated Vav1 as a Point of Integration for T-cell Receptor- and CD28-mediated Activation of JNK, p38, and Interleukin-2 Transcription. J. Biol. Chem. 275: 18160-18171 [Abstract] [Full Text]  
  • Bustelo, X. R. (2000). Regulatory and Signaling Properties of the Vav Family. Mol. Cell. Biol. 20: 1461-1477 [Full Text]  
  • De Sepulveda, P., Ilangumaran, S., Rottapel, R. (2000). Suppressor of Cytokine Signaling-1 Inhibits VAV Function through Protein Degradation. J. Biol. Chem. 275: 14005-14008 [Abstract] [Full Text]  
  • Ligensa, T., Krauss, S., Demuth, D., Schumacher, R., Camonis, J., Jaques, G., Weidner, K. M. (2001). A PDZ Domain Protein Interacts with the C-terminal Tail of the Insulin-like Growth Factor-1 Receptor but Not with the Insulin Receptor. J. Biol. Chem. 276: 33419-33427 [Abstract] [Full Text]  
  • Houlard, M., Arudchandran, R., Regnier-Ricard, F., Germani, A., Gisselbrecht, S., Blank, U., Rivera, J., Varin-Blank, N. (2002). Vav1 Is a Component of Transcriptionally Active Complexes. JEM 195: 1115-1127 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»