PMID- 10359597
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 10
IP  - 6
DP  - 1999 Jun
TI  - The small GTP-binding protein R-Ras can influence integrin activation by
      antagonizing a Ras/Raf-initiated integrin suppression pathway.
PG  - 1799-809
AB  - The rapid modulation of ligand-binding affinity ("activation") is a central
      property of the integrin family of cell adhesion receptors. The small GTP-binding
      protein Ras and its downstream effector kinase Raf-1 suppress integrin
      activation. In this study we explored the relationship between Ras and the
      closely related small GTP-binding protein R-Ras in modulating the integrin
      affinity state. We found that R-Ras does not seem to be a direct activator of
      integrins in Chinese hamster ovary cells. However, we observed that GTP-bound
      R-Ras strongly antagonizes the Ras/Raf-initiated integrin suppression pathway.
      Furthermore, this reversal of the Ras/Raf suppressor pathway does not seem to be 
      via a competition between Ras and R-Ras for common downstream effectors or via an
      inhibition of Ras/Raf-induced MAP kinase activation. Thus, R-Ras and Ras may act 
      in concert to regulate integrin affinity via the activation of distinct
      downstream effectors.
FAU - Sethi, T
AU  - Sethi T
AD  - Department of Respiratory Medicine, University of Edinburgh Medical School,
      Edinburgh EH8 9AG, United Kingdom.
FAU - Ginsberg, M H
AU  - Ginsberg MH
FAU - Downward, J
AU  - Downward J
FAU - Hughes, P E
AU  - Hughes PE
LA  - eng
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 Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Integrins)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ral GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - CHO Cells/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/genetics/metabolism
MH  - Cricetinae
MH  - GTP Phosphohydrolases/genetics/*metabolism
MH  - GTP-Binding Proteins/genetics/metabolism
MH  - Guanosine Triphosphate/metabolism
MH  - Integrins/*metabolism
MH  - Mitogen-Activated Protein Kinase 1
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
MH  - Proto-Oncogene Proteins c-raf/genetics/*metabolism
MH  - Suppression, Genetic
MH  - ral GTP-Binding Proteins
MH  - ras Proteins/genetics/*metabolism
PMC - PMC25373
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1091/mbc.10.6.1799 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1999 Jun;10(6):1799-809. doi: 10.1091/mbc.10.6.1799.