Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

Wu, Jui Chung; Chen, Yu Chen; Kuo, Chih Ting; Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean Cheng

doi:10.1038/srep18476

Cited by 58 publications

(50 citation statements)

References 60 publications

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“…Focal adhesion contacts are highly dynamic structures that undergo constant protein mobilization, assembly and disassembly during cell migration and spread and serve as spots for cross‐talk between actin and microtubule cytoskeletal networks . FAK is a signaling molecule that is known to be a key regulator of a number of cell functions, among which are cell spreading, migration, and survival and its signalling is known to be an important regulator of the ECM‐induced osteogenesis . Inhibition of FAK promotes focal adhesion maturation and reduces cell migration .…”

Section: Discussionmentioning

confidence: 99%

“…28 FAK is a signaling molecule that is known to be a key regulator of a number of cell functions, among which are cell spreading, migration, and survival and its signalling is known to be an important regulator of the ECM-induced osteogenesis. 30,31,[49][50][51][52][53] Inhibition of FAK promotes focal adhesion maturation and reduces cell migration. 51 Expectedly, nano-TiO 2 treated cells had a concentration-dependent decrease in the size of focal adhesions irrespective of the NP size.…”

Section: Discussionmentioning

confidence: 99%

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TiO₂ nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner

Ibrahim

Schoelermann

Mustafa

et al. 2018

J Biomedical Materials Res

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Human exposure to titanium dioxide nanoparticles (nano-TiO ) is increasing. An internal source of nano-TiO is represented by titanium-based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant-bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano-TiO on SaOS-2 human osteoblast-like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano-TiO . Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p-FAK ) and the expression of vinculin in response to nano-TiO were also assessed. Treatment with nano-TiO disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS-2 cells. The phosphorylation of p-FAK and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm-exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS-2 cells were affected by the selected nano-TiO in a size dependent manner. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2582-2593, 2018.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TiO₂ nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner

Ibrahim

Schoelermann

Mustafa

et al. 2018

J Biomedical Materials Res

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“…In addition to the SH2 domain mediated regulation for SRC focal adhesion targeting, our synthetic OS revealed that SRC oligomerization is a stabilizing process in adhesive sites mediated by SH3 domains. As a result, the apparent contradiction on the essential role of SH2 27 or SH3 28,29 domains in adhesive sites relocalization can now be explained if one assumes that the level of SRC oligomerization is considered since probably controlling specific partnership with a large repertoire of PRR-containing proteins present in adhesive sites. One hypothesis supported by this property is that controlling SH3 avidity or cooperativity by regulating SRC oligomerization is inducing an increase of their apparent 1 5 affinity leading to new binding as when a minimal level of multivalency of SH3 domains drives phase separation 30 .…”

Section: Engineering Synthetic Src To Understand Its Complex Structurmentioning

confidence: 99%

Molecular flux control encodes distinct cytoskeletal responses by specifying SRC signaling pathway usage

Kerjouan

Boyault

Oddou

et al. 2019

Preprint

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Multi-domain signaling proteins sample numerous stimuli to coordinate distinct cellular responses. Understanding the mechanisms of their pleiotropic signaling activity requires to directly manipulate their activity of decision leading to distinct cellular responses. We developed an optogenetic probe, optoSRC, to control spatio-temporally the SRC kinase, a representative example of versatile signaling node, and challenge its ability to generate different cellular responses. Genesis of different local molecular fluxes of the same optoSRC to adhesion sites, was sufficient to trigger distinct and specific acto-adhesive responses. Collectively, this study reveals how hijacking the pleiotropy of SRC signaling by modulating in space and time subcellular molecular fluxes of active SRC kinases.2 1

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“…Upstream activators of p38 include Src1 [27,28] and Rac1 [29,30]. Src1 is also a component of the focal adhesion complex [31]. The activation of PAR2 has been shown to result in the phosphorylation of p38 [32].…”

Section: Introductionmentioning

confidence: 99%

Accumulation of tissue factor in endothelial cells promotes cellular apoptosis through over-activation of Src1 and involves β1-integrin signalling

et al. 2019

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Accumulation of tissue factor (TF) within cells leads to cellular apoptosis mediated through p38 and p53 pathways. In this study, the involvement of Src1 in the induction of TF-mediated cell apoptosis, and the mechanisms of Src1 activation were investigated. Human coronary artery endothelial cell (HCAEC) were transfected with plasmids to express the wild-type TF (TF Wt-tGFP), or a mutant (Ser253 → Ala) which is incapable of being released from cells (TF Ala253-tGFP). The cells were then activated with PAR2-agonist peptide (SLIGKV-NH) and the phosphorylation of Src and Rac, and also the kinase activity of Src were assessed. Transfected cells were also pre-incubated with pp60c Src inhibitor, FAK inhibitor-14, or a blocking anti-β1-integrin antibody prior to activation and the phosphorylation of p38 as well as cellular apoptosis was examined. Finally, cells were co-transfected with the plasmids, together with a Src1-specific siRNA, activated as above and the cellular apoptosis measured. Activation of PAR2 lead to the phosphorylation of Src1 and Rac1 proteins at 60 min regardless of TF expression. Moreover, Src phosphorylation and kinase activity was prolonged up to 100 min in the presence of TF, with a significantly higher magnitude when the non-releasable TF Ala253-tGFP was expressed in HCAEC. Inhibition of Src with pp60c, or suppression of Src1 expression in cells, reduced p38 phosphorylation and prevented cellular apoptosis. In contrast, inhibition of FAK had no significant influence on Src kinase activity or cellular apoptosis. Finally, pre-incubation of cells with an inhibitory anti-β1-integrin antibody reduced both Src1 activation and cellular apoptosis. Our data show for the first time that the over-activation of Src1 is a mediator of TF-induced cellular apoptosis in endothelial cells through a mechanism that is dependent on its interaction with β1-integrin.

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Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

Cited by 58 publications

References 60 publications

TiO₂ nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner

TiO₂ nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner

Molecular flux control encodes distinct cytoskeletal responses by specifying SRC signaling pathway usage

Accumulation of tissue factor in endothelial cells promotes cellular apoptosis through over-activation of Src1 and involves β1-integrin signalling

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Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

Cited by 58 publications

References 60 publications

TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner

TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner

Molecular flux control encodes distinct cytoskeletal responses by specifying SRC signaling pathway usage

Accumulation of tissue factor in endothelial cells promotes cellular apoptosis through over-activation of Src1 and involves β1-integrin signalling

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TiO₂ nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner

TiO₂ nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner