PMID- 10652265
OWN - NLM
STAT- MEDLINE
DCOM- 20000412
LR  - 20220215
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 113 ( Pt 4)
DP  - 2000 Feb
TI  - TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct
      activation of rhoG.
PG  - 729-39
AB  - Rho GTPases regulate the morphology of cells stimulated by extracellular ligands.
      Their activation is controlled by guanine exchange factors (GEF) that catalyze
      their binding to GTP. The multidomain Trio protein represents an emerging class
      of &Rgr; regulators that contain two GEF domains of distinct specificities. We
      report here the characterization of Rho signaling pathways activated by the
      N-terminal GEF domain of Trio (TrioD1). In fibroblasts, TrioD1 triggers the
      formation of particular cell structures, similar to those elicited by RhoG, a
      GTPase known to activate both Rac1 and Cdc42Hs. In addition, the activity of
      TrioD1 requires the microtubule network and relocalizes RhoG at the active sites 
      of the plasma membrane. Using a classical in vitro exchange assay, TrioD1
      displays a higher GEF activity on RhoG than on Rac1. In fibroblasts, expression
      of dominant negative RhoG mutants totally abolished TrioD1 signaling, whereas
      dominant negative Rac1 and Cdc42Hs only led to partial and complementary
      inhibitions. Finally, expression of a Rho Binding Domain that specifically binds 
      RhoG(GTP) led to the complete abolition of TrioD1 signaling, which strongly
      supports Rac1 not being activated by TrioD1 in vivo. These data demonstrate that 
      Trio controls a signaling cascade that activates RhoG, which in turn activates
      Rac1 and Cdc42Hs.
FAU - Blangy, A
AU  - Blangy A
AD  - Centre de Recherche en Biochimie Macromoleculaire, CRBM CNRS UPR1086, IFR24,
      34293 Montpellier Cedex 5, France. blangy@crbm.cnrs-mop.fr
FAU - Vignal, E
AU  - Vignal E
FAU - Schmidt, S
AU  - Schmidt S
FAU - Debant, A
AU  - Debant A
FAU - Gauthier-Rouviere, C
AU  - Gauthier-Rouviere C
FAU - Fort, P
AU  - Fort P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actins)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Phosphoproteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Rhog protein, rat)
RN  - 0 (Transcription Factors)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Actins/analysis
MH  - Animals
MH  - Cells, Cultured
MH  - Fibroblasts/chemistry/enzymology/ultrastructure
MH  - *GTP Phosphohydrolases
MH  - Genes, Dominant
MH  - Genes, Reporter
MH  - Green Fluorescent Proteins
MH  - Guanosine Diphosphate/metabolism
MH  - Guanosine Triphosphate/metabolism
MH  - Indicators and Reagents/metabolism
MH  - Luminescent Proteins/genetics
MH  - Microscopy, Electron, Scanning
MH  - Microtubules/chemistry/metabolism
MH  - Mutagenesis/physiology
MH  - Peptide Fragments/metabolism
MH  - Phosphoproteins/analysis/chemistry/*metabolism
MH  - Protein Serine-Threonine Kinases/analysis/chemistry/*metabolism
MH  - Protein Structure, Tertiary
MH  - Rats
MH  - Recombinant Fusion Proteins/metabolism
MH  - Signal Transduction/physiology
MH  - Transcription Factors/analysis/genetics/*metabolism
MH  - Two-Hybrid System Techniques
MH  - Yeasts/genetics
MH  - cdc42 GTP-Binding Protein/antagonists & inhibitors/*metabolism
MH  - rac1 GTP-Binding Protein/antagonists & inhibitors/*metabolism
EDAT- 2000/02/01 09:00
MHDA- 2000/04/15 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/04/15 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1242/jcs.113.4.729 [doi]
PST - ppublish
SO  - J Cell Sci. 2000 Feb;113 ( Pt 4):729-39. doi: 10.1242/jcs.113.4.729.