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Cited by 341

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

VEGF-Induced Vascular Permeability Is Mediated by FAK

Open access
Chen, Xiao Lei, Nam, Ju-Ock, Jean, Christine, Lawson, Christine, Walsh, Colin T., Goka, Erik, Lim, Ssang-Taek, Tomar, Alok, Tancioni, Isabelle, Uryu, Sean, Guan, Jun-Lin, Acevedo, Lisette M., Weis, Sara M., Cheresh, David A., Schlaepfer, David D.·2012·Developmental Cell
DOI 10.1016/j.devcel.2011.11.002
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Abstract

SUMMARY Endothelial cells (ECs) form cell-cell adhesive junctional structures maintaining vascular integrity. This barrier is dynamically regulated by vascular endothelial growth factor (VEGF) receptor signaling. We created an inducible knockin mouse model to study the contribution of the integrin-associated focal adhesion tyrosine kinase (FAK) signaling on vascular function. Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation, rapid FAK localization to cell-cell junctions, binding of the FAK FERM domain to the vascular endothelial cadherin (VE-cadherin) cytoplasmic tail, and direct FAK phosphorylation of β-catenin at tyrosine-142 (Y142) facilitating VE-cadherin-β-catenin dissociation and EC junctional breakdown. Kinase inhibited FAK is in a closed conformation that prevents VE-cadherin association and limits VEGF-stimulated β-catenin Y142 phosphorylation. Our studies establish a role for FAK as an essential signaling switch within ECs regulating adherens junction dynamics.

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Metadata

Authors
Chen, X. L., Nam, J.-O., Jean, C., Lawson, C., Walsh, C. T., Goka, E., Lim, S.-T., Tomar, A., Tancioni, I., Uryu, S., Guan, J.-L., Acevedo, L. M., Weis, S. M., Cheresh, D. A., & Schlaepfer, D. D.
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2012-01
Volume
22
Issue
1
Pages
146-157
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2011.11.002
OpenAlex
W2028667039
Cited by
341
References
1
FWCI
19.83
Type
journal article
Language
en
Open access
bronze

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