PMID- 10570155
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 24
DP  - 1999 Nov 23
TI  - An Eph receptor regulates integrin activity through R-Ras.
PG  - 13813-8
AB  - The ability of integrins to mediate cell attachment to extracellular matrices and
      to blood proteins is regulated from inside the cell. Increased ligand-binding
      activity of integrins is critical for platelet aggregation upon blood clotting
      and for leukocyte extravasation to inflamed tissues. Decreased adhesion is
      thought to promote tumor cell invasion. R-Ras, a small intracellular GTPase,
      regulates the binding of integrins to their ligands outside the cell. Here we
      show that the Eph receptor tyrosine kinase, EphB2, can control integrin activity 
      through R-Ras. Cells in which EphB2 is activated become poorly adherent to
      substrates coated with integrin ligands, and a tyrosine residue in the R-Ras
      effector domain is phosphorylated. The R-Ras phosphorylation and loss of cell
      adhesion are causally related, because forced expression of an R-Ras variant
      resistant to phosphorylation at the critical site made cells unresponsive to the 
      anti-adhesive effect of EphB2. This is an unusual regulatory pathway among the
      small GTPases. Reduced adhesiveness induced through the Eph/R-Ras pathway may
      explain the repulsive effect of the Eph receptors in axonal pathfinding and may
      facilitate tumor cell invasion and angiogenesis.
FAU - Zou, J X
AU  - Zou JX
AD  - Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
FAU - Wang, B
AU  - Wang B
FAU - Kalo, M S
AU  - Kalo MS
FAU - Zisch, A H
AU  - Zisch AH
FAU - Pasquale, E B
AU  - Pasquale EB
FAU - Ruoslahti, E
AU  - Ruoslahti E
LA  - eng
GR  - HD25938/HD/NICHD NIH HHS/United States
GR  - F32 CA073195/CA/NCI NIH HHS/United States
GR  - P30 CA030199/CA/NCI NIH HHS/United States
GR  - P01 HD025938/HD/NICHD NIH HHS/United States
GR  - CA09579/CA/NCI NIH HHS/United States
GR  - CA79984/CA/NCI NIH HHS/United States
GR  - T32 CA009579/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Integrins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, EphB2)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Adhesion/physiology
MH  - Cell Line, Transformed
MH  - Chickens
MH  - Humans
MH  - Integrins/*metabolism
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Receptor, EphB2
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Signal Transduction
MH  - ras Proteins/genetics/*metabolism
PMC - PMC24147
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - 10.1073/pnas.96.24.13813 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13813-8. doi:
      10.1073/pnas.96.24.13813.