hSiah2 is a new vav binding protein which inhibits Vav-mediated signaling pathways

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)3798-3807
Number of pages10
JournalMolecular and Cellular Biology
Volume19
Issue number5
Publication statusPublished - May 1999

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NFATC Transcription Factors
Proteasome Endopeptidase Complex
T-Cell Antigen Receptor
Drosophila
Carrier Proteins
Photoreceptor Cells
src Homology Domains
Proto-Oncogenes
Heat-Shock Proteins
Guanosine Triphosphate
Protein Kinases
Cytoplasm
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Germani, A., Romero, F., Houlard, M., Camonis, J., Gisselbrecht, S., Fischer, S., & Varin-Blank, N. (1999). hSiah2 is a new vav binding protein which inhibits Vav-mediated signaling pathways. Molecular and Cellular Biology, 19(5), 3798-3807.

hSiah2 is a new vav binding protein which inhibits Vav-mediated signaling pathways. / Germani, Antonia; Romero, Francisco; Houlard, Martin; Camonis, Jacques; Gisselbrecht, Sylvie; Fischer, Siegmund; Varin-Blank, Nadine.

In: Molecular and Cellular Biology, Vol. 19, No. 5, 05.1999, p. 3798-3807.

Research output: Contribution to journalArticle

Germani, A, Romero, F, Houlard, M, Camonis, J, Gisselbrecht, S, Fischer, S & Varin-Blank, N 1999, 'hSiah2 is a new vav binding protein which inhibits Vav-mediated signaling pathways', Molecular and Cellular Biology, vol. 19, no. 5, pp. 3798-3807.
Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S et al. hSiah2 is a new vav binding protein which inhibits Vav-mediated signaling pathways. Molecular and Cellular Biology. 1999 May;19(5):3798-3807.
Germani, Antonia ; Romero, Francisco ; Houlard, Martin ; Camonis, Jacques ; Gisselbrecht, Sylvie ; Fischer, Siegmund ; Varin-Blank, Nadine. / hSiah2 is a new vav binding protein which inhibits Vav-mediated signaling pathways. In: Molecular and Cellular Biology. 1999 ; Vol. 19, No. 5. pp. 3798-3807.
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