PMID- 10364218
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 25
DP  - 1999 Jun 18
TI  - Morphological changes and detachment of adherent cells induced by p122, a
      GTPase-activating protein for Rho.
PG  - 17757-62
AB  - We recently cloned a novel signaling molecule, p122, that shows a
      GTPase-activating activity specific for Rho and the ability to enhance the
      phosphatidylinositol 4,5-bisphosphate-hydrolyzing activity of phospholipase C
      delta1 in vitro. Here we analyzed the in vivo function of p122. Microinjection of
      the GTPase-activating domain of p122 suppressed the formation of stress fibers
      and focal adhesions induced by lysophosphatidic acid, suggesting a
      GTPase-activating activity for Rho as in in vitro. Transfection of p122 also
      induced the disassembly of stress fibers and the morphological rounding of
      various adherent cells. Analyses using deletion and point mutants demonstrated
      that the GTPase-activating domain of p122 is responsible for the morphological
      changes and detachment and that arginine residues at positions 668 and 710 and a 
      lysine residue at position 706 in the GTPase-activating domain are essential.
      Using Fluo-3-based Ca2+ microscopy, we found that p122 evoked a rapid elevation
      of intracellular Ca2+ levels, suggesting that p122 stimulates the
      phosphatidylinositol 4, 5-bisphosphate-hydrolyzing activity of phospholipase C
      delta1. These results demonstrate that p122 synergistically functions as a
      GTPase-activating protein specific for Rho and an activator of phospholipase C
      delta1 in vivo and induces morphological changes and detachment through
      cytoskeletal reorganization.
FAU - Sekimata, M
AU  - Sekimata M
AD  - Department of Biomolecular Sciences, Institute of Biomedical Sciences, Fukushima 
      Medical College, 1 Hikariga-oka, Fukushima 960-1295, Japan.
FAU - Kabuyama, Y
AU  - Kabuyama Y
FAU - Emori, Y
AU  - Emori Y
FAU - Homma, Y
AU  - Homma Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Aniline Compounds)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Lysophospholipids)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Xanthenes)
RN  - 0 (rho GTPase-activating protein)
RN  - 23D4W0B50Y (Fluo-3)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.11 (Phospholipase C delta)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Aniline Compounds
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Line
MH  - Cell Size/drug effects
MH  - Cytoskeleton/metabolism
MH  - Enzyme Activation
MH  - GTP-Binding Proteins/*metabolism
MH  - *GTPase-Activating Proteins
MH  - Isoenzymes/metabolism
MH  - Lysophospholipids/pharmacology
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphatidylinositol 4,5-Diphosphate/metabolism
MH  - Phospholipase C delta
MH  - Plasmids
MH  - Transfection
MH  - Type C Phospholipases/metabolism
MH  - Xanthenes
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1074/jbc.274.25.17757 [doi]
AID - S0021-9258(19)72768-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 18;274(25):17757-62. doi: 10.1074/jbc.274.25.17757.