Src family kinases, key regulators of signal transduction

Parsons, Sarah J.; Parsons, J. Thomas

doi:10.1038/sj.onc.1208160

Cited by 821 publications

(693 citation statements)

References 7 publications

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“…An interesting exception to this rule is the knockout of Src -deletion of the most highly connected protein in the adhesome results in viable mice suffering only from osteopetrosis 29 . This may be explained by compensation provided by other Src family members such as Lyn and Fyn 30 .…”

Section: Characteristics Of the Adhesome Networkmentioning

confidence: 99%

Functional atlas of the integrin adhesome

Zaidel-Bar¹,

Itzkovitz²,

et al. 2007

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A detailed depiction of the 'integrin adhesome', consisting of a complex network of 156 components linked together and modified by 690 interactions is presented. Different views of the network reveal several functional 'subnets' that are involved in switching on or off many of the molecular interactions within the network, consequently affecting cell adhesion, migration and cytoskeletal organization. Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target. We discuss the role of the different network modules in regulating the structural and signalling functions of cell-matrix adhesions. Top-down and bottom-up approaches for studying the integrin adhesomeCell-extracellular matrix (ECM) interactions are mediated through specialized subcellular sites that contain specific adhesion receptors, cytoskeletal elements and a wide variety of interconnecting adaptor proteins [1][2][3] . These adhesion complexes permit cells to sense multiple extracellular signals that specify the chemical identity, geometry and physical properties of the ECM 4,5 . Thus, cells behave differently on two-and three-dimensional matrices 6 , distinguish between different ECM components 7 , can detect differences in adhesive ligand density 8 , and respond to mechanical perturbation and surface rigidity 9,10 . Competing Financial Interests:The authors declare no competing financial interests.Website -www.adhesome.org contains the adhesome database of components and interactions with an interface that allows dynamical navigation between hyperlinked subnets created for each component and for many network motifs within the adhesome network.Publisher's Disclaimer: Disclaimer: Nature Publishing Group has a collaboration with the Cell Migration Consortium for the creation and maintenance of the Cell Migration gateway (http://www.cellmigration.org/), but has no role in generating or curating the Cell Migration Consortium database content. As always, Nature Cell Biology Editors have been fully independent and solely responsible for the editorial content and peer review of this Analysis article. NIH Public Access Author ManuscriptNat Cell Biol. Author manuscript; available in PMC 2009 August 31. Published in final edited form as:Nat Cell Biol. 2007 August ; 9(8): 858-867. doi:10.1038/ncb0807-858. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTo understand the mechanisms underlying these diverse responses, in-depth characterization of individual proteins or pathways 11,12 , and collection of information about multiple components that concertedly form the presumed adhesome 13,14 , have been undertaken. Each of these approaches has limitations, and individually is unlikely to explain how the adhesion machinery senses environmental cues and responds to them. However, combining data from the two approaches could produce new mechanistic insights into the structu...

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Section: Characteristics Of the Adhesome Networkmentioning

confidence: 99%

Functional atlas of the integrin adhesome

Zaidel-Bar¹,

Itzkovitz²,

et al. 2007

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“…Several studies have shown that the non-receptor tyrosine kinase Src has important roles in numerous cellular processes, such as proliferation, survival, and cytoskeleton rearrangement [29]. Stimulation by 5-HT activated Src in endothelial cells through its receptor subtype HTR1B (Figs.…”

Section: -Ht Stimulates a Phosphorylation Signaling Cascade In Endotmentioning

confidence: 99%

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

Zamani

2012

FEBS Letters

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a b s t r a c tSerotonin, a known neurotransmitter, also functions as an angiokine to promote angiogenesis. The majority of serotonin in the human body is stored in platelets, and platelet aggregation leads to significant release of serotonin in thrombotic tumor environment. We have investigated serotonin signaling in human endothelial cells. Through G-protein-coupled receptors, serotonin at physiologically relevant concentrations activated Src/PI3K/AKT/mTOR/p70S6K phosphorylation signaling, and this activation was similar to that seen with VEGF. This finding provides insight into the overlapping angiogenic signaling pathways stimulated by serotonin in tumor environment, and suggests one of the mechanisms underlying resistance to current VEGF-targeting antiangiogenic therapy against cancer.

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“…Src family kinases (SFKs) comprise a subclass of membrane-associated non-receptor tyrosine kinases that are involved in a variety of cellular processes, such as cell division, motility, adhesion, angiogenesis and survival (5,6). Several of the SFKs have been shown to be upregulated in cancer and topromote progression and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma

Wang

Sun

et al. 2013

Oncology Reports

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Abstract. Src is an attractive target since it is overexpressed in a number of malignancies, including glioma. However, the mechanism of Src signaling as well as its silencing effect on temozolomide in glioma is not well known. We hypothesized that downregulation of Src may enhance the cytotoxic effect of temozolomide on glioma. As expected, Src was overexpressed in glioblastoma multiforme (GBM) compared with normal brain tissues. Src silencing suppressed tumor proliferation and induced apoptosis in glioma. In addition, Src silencing combined with temozolomide treatment resulted in significant inhibition of tumor growth. These effects may be mediated by AKT which is a downstream effector of Src, since downregulation of AKT exhibited a similar effect as Src siRNA when combined with temozolomide. Finally, we demonstrated that overexpression of AKT suppressed the enhanced cytotoxic effect of temozolomide mediated by Src silencing. Thus, the present study demonstrated that Src plays a biologically significant role in tumor proliferation and apoptosis and enhances the cytotoxic effect of temozolomide through AKT supression in glioma.

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Src family kinases, key regulators of signal transduction

Cited by 821 publications

References 7 publications

Functional atlas of the integrin adhesome

Functional atlas of the integrin adhesome

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

Downregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma

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