Targeting Vascular Cell Migration as a Strategy for Blocking Angiogenesis: The Central Role of Focal Adhesion Protein Tyrosine Kinase Family

Author(s): A. Angelucci , M. Bologna .

Journal Name: Current Pharmaceutical Design

Volume 13 , Issue 21 , 2007

Abstract:

The formation of capillary-like structures during angiogenesis requires a series of well-orchestrated cellular events allowing endothelial cells and pericytes to migrate into the perivascular space. The proper activation of the migratory machinery in these cells is fine controlled by the presence of angiogenic challenges and by the interactions with extracellular matrix. The two members of the focal adhesion protein tyrosine kinases (FA-PTKs), FAK and PYK2, play a central role in modulating endothelial and vascular smooth muscle cells migration confirming the well consolidated observations in other migrating cell types. However accumulating data reveal that FAK and PYK2 are involved in several cell processes including cell proliferation and survival. FAK, once localized to focal adhesions, is thought to be one of the principal effectors in linking signals initiated by integrins and growth factor receptors to cytoskeleton, thus controlling migration. Although more obscure, and differently regulated, the function of PYK2 seems to be similar to that of FAK, but restricted to few cell types, including vasculature forming cells. FAK and PYK2 exert a primary role as adaptor proteins able to recruit, with high turnover, several proteins which in turn, through their docking domains and tyrosine kinase activity, determine both the turnover in focal adhesion assembly and the specificity of downstream signaling. The characterization of functional interactions of FAPTKs may provide new potential therapeutic targets in order to control vascular pathological processes including angiogenesis.

Keywords: Focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (PYK2), focal adhesion, endothelial cells, vascular smooth muscle cells, vascular endothelial growth factor (VEGF), angiotensin II

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Article Details

VOLUME: 13
ISSUE: 21
Year: 2007
Page: [2129 - 2145]
Pages: 17
DOI: 10.2174/138161207781039643
Price: $58

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