PMID- 10022831
OWN - NLM
STAT- MEDLINE
DCOM- 19990426
LR  - 20181201
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 4
DP  - 1999 Feb 15
TI  - Role of alphavbeta3 integrin in the activation of vascular endothelial growth
      factor receptor-2.
PG  - 882-92
AB  - Interaction between integrin alphavbeta3 and extracellular matrix is crucial for 
      endothelial cells sprouting from capillaries and for angiogenesis. Furthermore,
      integrin-mediated outside-in signals co-operate with growth factor receptors to
      promote cell proliferation and motility. To determine a potential regulation of
      angiogenic inducer receptors by the integrin system, we investigated the
      interaction between alphavbeta3 integrin and tyrosine kinase vascular endothelial
      growth factor receptor-2 (VEGFR-2) in human endothelial cells. We report that
      tyrosine-phosphorylated VEGFR-2 co-immunoprecipitated with beta3 integrin
      subunit, but not with beta1 or beta5, from cells stimulated with VEGF-A165.
      VEGFR-2 phosphorylation and mitogenicity induced by VEGF-A165 were enhanced in
      cells plated on the alphavbeta3 ligand, vitronectin, compared with cells plated
      on the alpha5beta1 ligand, fibronectin or the alpha2beta1 ligand, collagen. BV4
      anti-beta3 integrin mAb, which does not interfere with endothelial cell adhesion 
      to vitronectin, reduced (i) the tyrosine phosphorylation of VEGFR-2; (ii) the
      activation of downstream transductor phosphoinositide 3-OH kinase; and (iii)
      biological effects triggered by VEGF-A165. These results indicate a new role for 
      alphavbeta3 integrin in the activation of an in vitro angiogenic program in
      endothelial cells. Besides being the most important survival system for nascent
      vessels by regulating cell adhesion to matrix, alphavbeta3 integrin participates 
      in the full activation of VEGFR-2 triggered by VEGF-A, which is an important
      angiogenic inducer in tumors, inflammation and tissue regeneration.
FAU - Soldi, R
AU  - Soldi R
AD  - Institute for Cancer Research and Treatment (IRCC), Biology and Biochemistry,
      School of Medicine, University of Torino, 10100 Torino, Italy.
FAU - Mitola, S
AU  - Mitola S
FAU - Strasly, M
AU  - Strasly M
FAU - Defilippi, P
AU  - Defilippi P
FAU - Tarone, G
AU  - Tarone G
FAU - Bussolino, F
AU  - Bussolino F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Androstadienes)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Receptors, Vitronectin)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
SB  - S
MH  - Androstadienes/pharmacology
MH  - Antibodies, Monoclonal/pharmacology
MH  - Cells, Cultured
MH  - Endothelial Growth Factors/pharmacology
MH  - Endothelium, Vascular/*metabolism
MH  - Enzyme Activation
MH  - Extracellular Matrix/metabolism
MH  - Humans
MH  - Lymphokines/pharmacology
MH  - Membrane Proteins/metabolism
MH  - Neovascularization, Physiologic
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine/analysis
MH  - Precipitin Tests
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Growth Factor/*metabolism
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Receptors, Vitronectin/immunology/*metabolism
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
MH  - Wortmannin
PMC - PMC1171181
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1093/emboj/18.4.882 [doi]
PST - ppublish
SO  - EMBO J. 1999 Feb 15;18(4):882-92. doi: 10.1093/emboj/18.4.882.