The antagonistic roles of PDGF and integrin αvβ3 in regulating ROS production at focal adhesions

Abstract Reactive oxygen species (ROS) have been shown to play crucial roles in regulating various cellular functions, e.g. focal adhesion (FA) dynamics and cell migration upon growth factor stimulation. However, it is not clear how ROS are regulated at subcellular FA sites to impact cell migration....

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Bibliographic Details
Published in:Biomaterials 2013-05, Vol.34 (15), p.3807-3815
Main Authors: Lin, Li-Jung, Grimme, Jill M, Sun, Jie, Lu, Shaoying, Gai, Lisa, Cropek, Donald M, Wang, Yingxiao
Format: Article
Language:English
Subjects:
Advanced Basic Science
Amino Acid Sequence
Animals
Biosensing Techniques
Cytosol - metabolism
Dentistry
Fluorescence Resonance Energy Transfer
Fluorescence resonance energy transfer (FRET)
Focal adhesion (FA)
Focal Adhesions - drug effects
Focal Adhesions - metabolism
HEK293 Cells
Humans
Integrin
Integrin alphaVbeta3 - antagonists & inhibitors
Integrin alphaVbeta3 - metabolism
Mice
Models, Biological
Molecular Sequence Data
Platelet derived growth factor (PDGF)
Platelet-Derived Growth Factor - antagonists & inhibitors
Platelet-Derived Growth Factor - metabolism
Platelet-Derived Growth Factor - pharmacology
rac1 GTP-Binding Protein - metabolism
Reactive oxygen species (ROS)
Reactive Oxygen Species - metabolism
rhoA GTP-Binding Protein - metabolism
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Summary:Abstract Reactive oxygen species (ROS) have been shown to play crucial roles in regulating various cellular functions, e.g. focal adhesion (FA) dynamics and cell migration upon growth factor stimulation. However, it is not clear how ROS are regulated at subcellular FA sites to impact cell migration. We have developed a biosensor capable of monitoring ROS production at FA sites in live cells with high sensitivity and specificity, utilizing fluorescence resonance energy transfer (FRET). The results revealed that platelet derived growth factor (PDGF) can induce ROS production at FA sites, which is mediated by Rac1 activation. In contrast, integrins, specifically integrin αvβ3, inhibits this local ROS production. The RhoA activity can mediate this inhibitory role of integrins in regulating ROS production. Therefore, PDGF and integrin αvβ3 coordinate to have an antagonistic effect in the ROS production at FA sites to regulate cell adhesion and migration.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.01.092