PMID- 10523675
OWN - NLM
STAT- MEDLINE
DCOM- 19991124
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 11
DP  - 1999 Nov
TI  - Biological and regulatory properties of Vav-3, a new member of the Vav family of 
      oncoproteins.
PG  - 7870-85
AB  - We report here the identification and characterization of a novel Vav family
      member, Vav-3. Signaling experiments demonstrate that Vav-3 participates in
      pathways activated by protein tyrosine kinases. Vav-3 promotes the exchange of
      nucleotides on RhoA, on RhoG and, to a lesser extent, on Rac-1. During this
      reaction, Vav-3 binds physically to the nucleotide-free states of those GTPases. 
      These functions are stimulated by tyrosine phosphorylation in wild-type Vav-3 and
      become constitutively activated upon deletion of the entire calponin-homology
      region. Expression of truncated versions of Vav-3 leads to drastic actin
      relocalization and to the induction of stress fibers, lamellipodia, and membrane 
      ruffles. Moreover, expression of Vav-3 alters cytokinesis, resulting in the
      formation of binucleated cells. All of these responses need only the expression
      of the central region of Vav-3 encompassing the Dbl homology (DH), pleckstrin
      homology (PH), and zinc finger (ZF) domains but do not require the presence of
      the C-terminal SH3-SH2-SH3 regions. Studies conducted with Vav-3 proteins
      containing loss-of-function mutations in the DH, PH, and ZF regions indicate that
      only the DH and ZF regions are essential for Vav-3 biological activity. Finally, 
      we show that one of the functions of the Vav-3 ZF region is to work coordinately 
      with the catalytic DH region to promote both the binding to GTP-hydrolases and
      their GDP-GTP nucleotide exchange. These results highlight the role of Vav-3 in
      signaling and cytoskeletal pathways and identify a novel functional cross-talk
      between the DH and ZF domains of Vav proteins that is imperative for the binding 
      to, and activation of, Rho GTP-binding proteins.
FAU - Movilla, N
AU  - Movilla N
AD  - Department of Pathology, State University of New York at Stony Brook, University 
      Hospital, Stony Brook, New York 11794-7025, USA.
FAU - Bustelo, X R
AU  - Bustelo XR
LA  - eng
SI  - GENBANK/AF118886
SI  - GENBANK/AF118887
GR  - CA7373501/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Blood Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (MCF2 protein, human)
RN  - 0 (Mcf2 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (Recombinant Proteins)
RN  - 0 (VAV3 protein, human)
RN  - 0 (Vav3 protein, mouse)
RN  - 0 (platelet protein P47)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
SB  - IM
MH  - 3T3 Cells/cytology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Blood Proteins/genetics
MH  - Cell Compartmentation
MH  - *Cell Cycle Proteins
MH  - Cell Transformation, Neoplastic
MH  - Guanine Nucleotide Exchange Factors/genetics/isolation & purification/*metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Multigene Family
MH  - *Phosphoproteins
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-vav
MH  - Recombinant Proteins/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Tissue Distribution
MH  - Zinc Fingers/genetics
MH  - rho GTP-Binding Proteins/metabolism
PMC - PMC84867
EDAT- 1999/10/19 00:00
MHDA- 1999/10/19 00:01
CRDT- 1999/10/19 00:00
PHST- 1999/10/19 00:00 [pubmed]
PHST- 1999/10/19 00:01 [medline]
PHST- 1999/10/19 00:00 [entrez]
AID - 10.1128/mcb.19.11.7870 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Nov;19(11):7870-85. doi: 10.1128/mcb.19.11.7870.