PMID- 10655584
OWN - NLM
STAT- MEDLINE
DCOM- 20000320
LR  - 20121115
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 2
IP  - 2
DP  - 2000 Feb
TI  - Activation of EphA2 kinase suppresses integrin function and causes
      focal-adhesion-kinase dephosphorylation.
PG  - 62-9
AB  - Interactions between receptor tyrosine kinases of the Eph family and their
      ligands, ephrins, are implicated in establishment of organ boundaries and
      repulsive guidance of cell migration during development, but the mechanisms by
      which this is achieved are unclear. Here we show that activation of endogenous
      EphA2 kinase induces an inactive conformation of integrins and inhibits cell
      spreading, migration and integrin-mediated adhesion. Moreover, EphA2 is
      constitutively associated with focal-adhesion kinase (FAK) in resting cells.
      Within one minute after stimulation of EphA2 with its ligand, ephrin-A1, the
      protein tyrosine phosphatase SHP2 is recruited to EphA2; this is followed by
      dephosphorylation of FAK and paxillin, and dissociation of the FAK-EphA2 complex.
      We conclude that Eph kinases mediate some of their functions by negatively
      regulating integrins and FAK.
FAU - Miao, H
AU  - Miao H
AD  - Rammelkamp Center for Research, MetroHealth Campus, Case Western Reserve
      University School of Medicine, 2500 MetroHealth Drive, Cleveland, Ohio 44109,
      USA.
FAU - Burnett, E
AU  - Burnett E
FAU - Kinch, M
AU  - Kinch M
FAU - Simon, E
AU  - Simon E
FAU - Wang, B
AU  - Wang B
LA  - eng
GR  - P50 DK54178/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Ephrin-A1)
RN  - 0 (Integrins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, EphA2)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (PTK2 protein, human)
RN  - EC 2.7.10.2 (Ptk2 protein, mouse)
RN  - EC 3.1.3.48 (PTPN11 protein, human)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Ptpn11 protein, mouse)
RN  - EC 3.1.3.48 (Ptpn6 protein, mouse)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - COS Cells
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Movement
MH  - Cell Size
MH  - Enzyme Activation
MH  - Ephrin-A1
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Humans
MH  - Integrins/*metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ligands
MH  - Mice
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/antagonists & inhibitors/metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proteins/pharmacology
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptor, EphA2
EDAT- 2000/02/03 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/02/03 09:00
PHST- 2000/02/03 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/02/03 09:00 [entrez]
AID - 10.1038/35000008 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2000 Feb;2(2):62-9. doi: 10.1038/35000008.