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Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha(2)beta(1)integrin (CROSBI ID 210928)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Bix, Gregory ; ... ; Campbell, Shelly ; Zutter, Mary M. ; Santoro, Samuel A. ; Kim, Jiyeun K. ; Höök, Magnus ; Reed, Charles C. ; Iozzo, Renato V. Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha(2)beta(1)integrin // The Journal of cell biology, 166 (2004), 1; 97-109. doi: 10.1083/jcb.200401150

Podaci o odgovornosti

Bix, Gregory ; ... ; Campbell, Shelly ; Zutter, Mary M. ; Santoro, Samuel A. ; Kim, Jiyeun K. ; Höök, Magnus ; Reed, Charles C. ; Iozzo, Renato V.

engleski

Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha(2)beta(1)integrin

Endorepellin, the COOH-terminal domain of the heparan sulfate proteoglycan perlecan, inhibits several aspects of angiogenesis. We provide evidence for a novel biological axis that links a soluble fragment of perlecan protein core to the major cell surface receptor for collagen alpha(2)beta(1)integrin, and provide an initial investigation of the intracellular signaling events that lead to endorepellin antiangiogenic activity. The interaction between endorepellin and integrin triggers a unique signaling pathway that causes an increase in the second messenger cAMP ; activation of two proximal kinases, protein kinase A and focal adhesion kinase ; transient activation of p38 mitogen-activated protein kinase and heat shock protein 27, followed by a rapid down-regulation of the latter two proteins ; and ultimately disassembly of actin stress fibers and focal adhesions. The end result is a profound block of endothelial cell migration and angiogenesis. Because perlecan is present in both endothelial and smooth muscle cell basement membranes, proteolytic activity during the initial stages of angiogenesis could liberate antiangiogenic fragments from blood vessels’ walls, including endorepellin.

Actins/metabolism; Cytoskeleton/metabolism; Endothelium; Vascular/cytology; Protein-Tyrosine Kinases/metabolism

Shelly Pranić je rođena Shelly Campbell

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Podaci o izdanju

166 (1)

2004.

97-109

objavljeno

0021-9525

10.1083/jcb.200401150

Povezanost rada

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Temeljne medicinske znanosti, Biologija

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