Reactive oxygen species activate focal adhesion kinase, paxillin and P130CAS tyrosine phosphorylation in endothelial cells

Gozin, Alexia; Franzini, E.; Andrieu, Valérie; Costa, Lydie Da; Rollet-Labelle, Emmanuelle; Pasquier, Claude

doi:10.1016/s0891-5849(98)00134-8

Cited by 86 publications

(56 citation statements)

References 48 publications

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“…Furthermore, p125FAK regulates interactions of integrins with the cytoskeleton and with the extracellular matrix or both. Thus, stimulation of p125FAK by ROS mediates reversible changes in cell shape and morphology, reorganisation of the cytoskeleton and redistribution of cell-surface adhesion proteins [119]. The involvement of high glucose concentration in ROS and tyrosine kinase activation hyperglycaemia is further supported by findings that genistein, an antioxidant and non-selective inhibitor of tyrosine kinases, prevented glucosemediated atherogenic modification of low density lipoprotein [120].…”

Section: Nomentioning

confidence: 86%

“…In addition to p60Src, p56Lck, p59Fyn, Syk, ZAP-70 [13] and the Ca 2+ -sensitive proline-rich tyrosine kinase Pyk2 [118] are also affected by ROS. In ROS-treated endothelial cells tyrosine phosphorylation of the Pyk2 downstream target p130cas, of a focal adhesion kinase (p125FAK) and of paxillin is increased [119]. The cytosolic tyrosine kinase p125FAK, a non-receptor protein-tyrosine kinase, plays a central role in the regulation of the actin cytoskeletal organisation by phosphorylating components of focal adhesion, such as tensin, paxillin and talin.…”

Section: Nomentioning

confidence: 99%

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Vascular targets of redox signalling in diabetes mellitus

2002

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There is overwhelming evidence for an involvement of reactive oxygen species (ROS) in the pathogenesis of diabetes-associated vascular complications. However, neither the exact source of the ROS initiating cascades leading to cell dysfunction in diabetes nor their chemical nature is fully understood. Furthermore, despite our knowledge of the crucial role of ROS in diabetes, little is known about the actual targets and the molecular consequences of the interaction of ROS with cellular signalling pathways.Therefore, we aim to provide an overview of ROS (i. e. O 2 · , NO · , ONOO  and H 2 O 2 ) and their vascular sources in diabetes and to summarise recent knowledge on the mechanisms underlying increased ROS production within the vascular wall. In addition, possible targets of diabetes and ROS within the vasculature are discussed. These include, the effects of ROS on small guanine nucleotide binding proteins, the cytoskeleton, protein kinases (e. g. tyrosine kinases), metalloproteinases, ion homeostasis and transcriptional regulation.Such analysis makes it clear that the generation of ROS could affect a large number of various signalling pathways and proteins. Thus, a better knowledge of the functional diversity and pathological consequences of each individual pathway activated by ROS is essential to understand the mechanisms of diabetesassociated vascular complications. [Diabetologia (2002) 45:476±494]

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Section: Nomentioning

confidence: 86%

Section: Nomentioning

confidence: 99%

Vascular targets of redox signalling in diabetes mellitus

2002

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“…This enzyme that generates superoxide and other systems that produce free radicals, including hydrogen peroxide and the hydroxyl radical, may itself be able to influence the function of CAS. Gozin et al (11) reported that the hydroxyl radical increased tyrosyl-phosphorylation of CAS in endothelial cells, an event that would facilitate the activation of signaling pathways. Moreover, Src and CAS mediation of JNK activation was driven by reactive oxygen species (50).…”

Section: Pathway For Cas-mediated 5-ht-induced Contractionmentioning

confidence: 99%

A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction

Ogden

Thompson

Hickner

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Am J Physiol Heart Circ Physiol 291: H2857-H2863, 2006. First published July 21, 2006 doi:10.1152/ajpheart.00229.2006.-Crkassociated substrate (CAS), a 130-kDa adaptor protein, was discovered as a tyrosine kinase substrate of Src that was important to cellular motility and actin filament formation. As the tyrosine kinase Src is utilized by the 5-hydroxytryptamine (5-HT)2A receptor in arterial contraction, we tested the hypothesis that CAS was integral to 5-HT2A receptor-mediated vasoconstriction. Rat thoracic aorta was used as a model of the arterial 5-HT2A receptor. Western and immunohistochemistry analyses validated the presence of CAS in the aorta, and tissue bath experiments demonstrated reduction of contraction to 5-HT (13.5 Ϯ 5% control maximum) and the 5-HT2 receptor agonist ␣-methyl-5-HT (6 Ϯ 2% maximum) by latrunculin B (10 Ϫ6 mol/l), an actin disruptor. In aorta contracted with 5-HT (10 Ϫ5 mol/l), tyrosine phosphorylation (Tyr410) of CAS was significantly increased (ϳ225%), and both contraction and CAS phosphorylation were reduced by the 5-HT2A/2C receptor antagonist ketanserin (3 ϫ 10 Ϫ8 mol/l). Src is one candidate for 5-HT-stimulated CAS tyrosyl-phosphorylation as 5-HT promoted interaction of Src and CAS in coimmunoprecipitation experiments, and the Src tyrosine kinase inhibitor PP1 (10 Ϫ5 mol/l) abolished 5-HT-induced tyrosyl-phosphorylation of CAS and reduced 5-HT-and ␣-methyl-5-HT-induced contraction. Antisense oligodeoxynucleotides delivered to the aorta reduced CAS expression (33% control) and arterial contraction to ␣-methyl-5-HT (45% of control), independent of changes in myosin light chain phosphorylation. These data are the first to implicate CAS in the signal transduction of 5-HT. 5-hydroxytryptamine; antisense oligodeoxynucleotides; signal transduction; Src THE ACTIVATION of protein kinases in phosphorylation cascades is critical to signal transduction. This process is facilitated by adaptor proteins that contain Src homology 2 (SH2) and Src homology 3 (SH3) protein regions that allow for docking of other proteins and facilitation of protein-protein interactions. One such adapter protein is Crk-associated substrate or CAS (also known as p130 or p130 CAS). This 130-kDa protein has been recognized as a substrate for the tyrosine kinase Crk (23), and CAS is highly tyrosine phosphorylated in response to activation of Crk or Src (25,26). Docking of and tyrosylphosphorylation by these proteins, as well as other regulators, including focal adhesion kinase (FAK) and protein tyrosine phosphatase 1B (PTP1B), enables CAS to participate in important physiological events, including cell migration (14, 18, 27), mitosis (30), adhesion (42), and apoptosis (48).The involvement of CAS in contraction is logical because CAS is essential for actin filament reorganization (12, 38). CAS is a regulator of the actin-associated protein profilin (14), which is necessary for actin-filament polymerization in smooth muscl...

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“…Therefore, it is likely that oxidative stress-induced Src activation leads to FAK activation and promotion of cell migration. Oxidative stress-induced activation of FAK and promotion of cell motility has been seen in endothelial cells (7,27). Reactive oxygen species, including hydrogen peroxide, appear to be involved in vascular remodeling in hypertension (28) and myocardial injury (5).…”

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confidence: 99%

Hydrogen peroxide activates focal adhesion kinase and c-Src by a phosphatidylinositol 3 kinase-dependent mechanism and promotes cell migration in Caco-2 cell monolayers

Basuroy

Dunagan

Sheth

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Basuroy S, Dunagan M, Sheth P, Seth A, Rao RK. Hydrogen peroxide activates focal adhesion kinase and c-Src by a phosphatidylinositol 3 kinase-dependent mechanism and promotes cell migration in Caco-2 cell monolayers. Am J Physiol Gastrointest Liver Physiol 299: G186-G195, 2010. First published April 8, 2010 doi:10.1152/ajpgi.00368.2009.-Recent studies showed that c-Src and phosphatidylinositol 3 (PI3) kinase mediate the oxidative stress-induced disruption of tight junctions in Caco-2 cell monolayers. The present study evaluated the roles of PI3 kinase and Src kinase in the oxidative stress-induced activation of focal adhesion kinase (FAK) and acceleration of cell migration. Oxidative stress, induced by xanthine and xanthine oxidase system, rapidly increased phosphorylation of FAK on Y397, Y925, and Y577 in the detergent-insoluble and soluble fractions and increased its tyrosine kinase activity. The PI3 kinase inhibitors, wortmannin and LY294002, and the Src kinase inhibitor, 4-amino-5[chlorophyll]-7-[tbutyl]pyrazolo [3-4-d]pyrimidine, attenuated tyrosine phosphorylation of FAK. Oxidative stress induced phosphorylation of c-Src on Y418 by a PI3 kinase-dependent mechanism, whereas oxidative stress-induced activation of PI3 kinase was independent of Src kinase activity. Hydrogen peroxide accelerated Caco-2 cell migration in a concentration-dependent manner. Promotion of cell migration by hydrogen peroxide was attenuated by LY294002 and PP2. Reduced expression of FAK by siRNA attenuated hydrogen peroxide-induced acceleration of cell migration. The expression of constitutively active c-Src Y527F enhanced cell migration, whereas the expression of dominant negative c-Src K296R/Y528F attenuated hydrogen peroxide-induced stimulation of cell migration. Oxidative stress-induced activation of c-Src and FAK was associated with a rapid increase in the tyrosine phosphorylation and the levels of paxillin and p130 CAS in actin-rich, detergent-insoluble fractions. This study shows that oxidative stress activates FAK and accelerates cell migration in an intestinal epithelium by a PI3 kinase-and Src kinase-dependent mechanism. epithelium; barrier function; cell motility; protein phosphorylation A SIGNIFICANT BODY OF EVIDENCE indicates that oxidative stress disrupts epithelial tight junctions and adherens junctions, leading to an increase in the paracellular permeability in Caco-2 and Madin-Darby canine kidney (MDCK) cell monolayers (16 -19). Oxidative stress induces tyrosine phosphorylation of a wide spectrum of proteins, including occludin, zonula occludens-1, E-cadherin, and ␤-catenin and tyrosine kinase inhibitors attenuate the oxidative stress-induced increase in paracellular permeability (1,16,19). Previous studies demonstrated that oxidative stress activates c-Src and phosphatidylinositol (PI3) kinase, and these activities are involved in the oxidative stress-induced disruption of tight junctions and increase in paracellular permeability in Caco-2 and MDCK cell monolayers (2, 23).Focal adhesion kinase (FAK) plays an importan...

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Reactive oxygen species activate focal adhesion kinase, paxillin and P130CAS tyrosine phosphorylation in endothelial cells

Cited by 86 publications

References 48 publications

Vascular targets of redox signalling in diabetes mellitus

Vascular targets of redox signalling in diabetes mellitus

A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction

Hydrogen peroxide activates focal adhesion kinase and c-Src by a phosphatidylinositol 3 kinase-dependent mechanism and promotes cell migration in Caco-2 cell monolayers

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