Focal adhesion kinase regulation of neovascularization

Microvasc Res. 2012 Jan;83(1):64-70. doi: 10.1016/j.mvr.2011.05.002. Epub 2011 May 14.

Abstract

In this review, we discuss the role of focal adhesion kinase (FAK), an intracellular tyrosine kinase, in endothelial cells in relation to neovascularization. Genetic and in vitro studies have identified critical factors, receptor systems, and their intracellular signaling components that regulate the neovasculogenic phenotypes of endothelial cells. Among these factors, FAK appears to regulate several aspects of endothelial cellular behavior, including migration, survival, cytoskeletal organization, as well as cell proliferation. Upon adhesion of endothelial cells to extracellular matrix (ECM) ligands, integrins cluster on the plane of plasma-membrane, while cytoplasmic domains of integrins interact with cytoskeletal proteins and signaling molecules including FAK. However, FAK not only serves as a critical component of integrin signaling, but is also a downstream element of the VEGF/VEGF-receptor and other ligand-receptor systems that regulate neovascularization. A complete understanding of FAK-mediated neovascularization, therefore, should address the molecular and cellular mechanisms that regulate the biology of FAK. Continued research on FAK may, therefore, yield novel therapies to improve treatment modalities for the pathological neovascularization associated with diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Endothelial Cells / enzymology*
  • Endothelial Cells / pathology
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Focal Adhesions / enzymology*
  • Focal Adhesions / pathology
  • Humans
  • Neoplasms / blood supply*
  • Neovascularization, Pathologic / enzymology*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Physiologic*
  • Signal Transduction

Substances

  • Focal Adhesion Protein-Tyrosine Kinases