PMID- 10207103
OWN - NLM
STAT- MEDLINE
DCOM- 19990518
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 5
DP  - 1999 May
TI  - hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling
      pathways.
PG  - 3798-807
AB  - 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.
FAU - Germani, A
AU  - Germani A
AD  - Institut Cochin de Genetique Moleculaire, U363 INSERM, Hopital Cochin, Universite
      Paris V, 75014 Paris, France. germani@cochin.inserm.fr
FAU - Romero, F
AU  - Romero F
FAU - Houlard, M
AU  - Houlard M
FAU - Camonis, J
AU  - Camonis J
FAU - Gisselbrecht, S
AU  - Gisselbrecht S
FAU - Fischer, S
AU  - Fischer S
FAU - Varin-Blank, N
AU  - Varin-Blank N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Transcription Factors)
RN  - 0 (VAV1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (seven in absentia proteins)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/genetics/metabolism
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Enzyme Activation
MH  - Fluorescent Antibody Technique
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Jurkat Cells
MH  - *Mitogen-Activated Protein Kinases
MH  - NFATC Transcription Factors
MH  - Nuclear Proteins/*metabolism
MH  - Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-vav
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic
MH  - Transfection
MH  - Ubiquitin-Protein Ligases
PMC - PMC84217
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - 10.1128/mcb.19.5.3798 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 May;19(5):3798-807. doi: 10.1128/mcb.19.5.3798.