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PMID: 10207103 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular and cellular biology ·Vol. 19 ·No. 5 ·1999-05-00 ·Pages 3798-807

Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N

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.

MeSH Terms
Animals COS Cells Calcium-Calmodulin-Dependent Protein Kinases/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Enzyme Activation Fluorescent Antibody Technique Genes, Reporter/genetics Humans JNK Mitogen-Activated Protein Kinases Jurkat Cells Mitogen-Activated Protein Kinases NFATC Transcription Factors Nuclear Proteins/metabolism Oncogene Proteins/metabolism Proto-Oncogene Mas Proto-Oncogene Proteins c-vav Receptors, Antigen, T-Cell/metabolism Transcription Factors/genetics,metabolism Transcription, Genetic Transfection Ubiquitin-Protein Ligases
Chemicals
DNA-Binding Proteins MAS1 protein, human NFATC Transcription Factors Nuclear Proteins Oncogene Proteins Proto-Oncogene Mas Proto-Oncogene Proteins c-vav Receptors, Antigen, T-Cell Transcription Factors VAV1 protein, human Ubiquitin-Protein Ligases seven in absentia proteins Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Germani A
Institut Cochin de Génétique Moléculaire, U363 INSERM, Hôpital Cochin, Université Paris V, 75014 Paris, France. germani@cochin.inserm.fr
Romero F
Houlard M
Camonis J
Gisselbrecht S
Fischer S
Varin-Blank N
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.5.3798
Email
germani@cochin.inserm.fr
Published
1999-05-00
Pages
3798-807
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84217
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.19.5.3798 PMC Full Text View journal details
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