Negative regulation of EGFR signalling through integrin-α1β1-mediated activation of protein tyrosine phosphatase TCPTP

Mattila, Eero; Pellinen, Teijo; Nevo, Jonna; Vuoriluoto, Karoliina; Arjonen, Antti; Ivaska, Johanna

doi:10.1038/ncb1209

Cited by 185 publications

(178 citation statements)

References 29 publications

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“…Integrin b1-mediated cell adhesion regulates a multitude of cellular responses, including proliferation, survival and cross-talk between different cellular signaling pathways. A collagen-binding integrin a1b1 functions as a negative regulator of epidermal growth factor receptor (EGFR) signaling through the activation of a protein tyrosine phosphatase [22,23]. Integrinmediated cell-ECM interactions play a critical role in cell adhesion, migration and morphogenesis during vertebrate retinal development [24].…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

et al. 2005

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Summaryp37 protein is a membrane lipoprotein of Mycoplasma hyorhinis, and our previous work showed that there was high ratio of M. hyorhinis infection in human gastric carcinoma. To investigate the possible functions of p37 in cancer development, the nucleotide sequence of p37 gene was modified and expressed well in transfected cells. We found that p37 localized at the Golgi apparatus and could be secreted out of the cell. Human gastric cancer cells AGS, after being transfected with the p37 gene, were smaller, more spherical and easy to detach from each other. Their adhesion to matrix was also diminished and cytoskeleton in these stable p37 AGS cell was rearranged and transcription co-factor b-actin was transferred to nucleolus with down-regulation of ICAM-1 and integrin b1. These findings will be helpful for us to elucidate the effects of p37 on eukaryotic cells as well as to better understand the potential relationship between cancer and mycoplasma infection.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

et al. 2005

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“…It is the charged chemical nature of spermidine that is thought to play a critical role in the biological activity of the compound, including its activating effect on various enzymes like TCPTP (14,24,25). Although the proposed mechanism by which spermidine increases TCPTP activity has not been clearly defined, it is known that spermidine interacts with TCPTP at the same site as the ␣ 1 -integrin cytoplasmic tail residues 1164 -1179 identified previously to activate TCPTP (6,14). One current hypothesis suggests that the polycationic character of spermidine is responsible for breaking an autoregulatory intramolecular bond between the carboxy-terminal and catalytic domain in TCPTP (14).…”

Section: Discussionmentioning

confidence: 99%

“…PTPs play an integral role in regulating a variety of basic cellular processes, including cell growth and differentiation (5). Among TCPTP substrates are the phosphotyrosine residues on the receptors for epidermal growth factor (6) and insulin (7). Additionally, TCPTP negatively regulates phosphorylation of the IFN-␥ receptor (IFN␥R) and the IFN-␥ signaling molecules signal transducers and activators of transcription (STAT) 1 and 3 (8, 9).…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Spermidine Stimulates T Cell Protein-tyrosine Phosphatase-mediated Protection of Intestinal Epithelial Barrier Function

Penrose

Marchelletta

Krishnan

et al. 2013

Journal of Biological Chemistry

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Background: TCPTP is a negative regulator of proinflammatory cytokine signaling and may be a therapeutic target for IBD. Results: Administration of spermidine to intestinal epithelial cells reduced proinflammatory cytokine signaling and subsequent barrier defects in a TCPTP-dependent manner. Conclusion: Activation of TCPTP by spermidine attenuates inflammatory responses in intestinal epithelial monolayers. Significance: Protection of epithelial barrier integrity by spermidine in vitro suggests its potential importance for barrier protection in vivo.

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“…Activation of Rac1 can be mediated by multiple mechanisms, including activation of tyrosine kinase receptors, such as the EGFR (38,51). It has been shown that loss of integrin ␣1␤1 leads to upregulated EGFR tyrosine phosphorylation (39). In addition, ROS can initiate a number of physiological responses, including tyrosine phosphorylation of growth factor receptors, such as platelet-derived growth factor receptor and EGFR (23).…”

Section: Fig 7 Ros Partially Contribute To Increased Egfr Phosphorymentioning

confidence: 99%

Integrin α1β1 Controls Reactive Oxygen Species Synthesis by Negatively Regulating Epidermal Growth Factor Receptor-Mediated Rac Activation

Chen¹,

Abair²,

Ibanez³

et al. 2007

Molecular and Cellular Biology

100

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Integrins control many cell functions, including generation of reactive oxygen species (ROS) and regulation of collagen synthesis. Mesangial cells, found in the glomerulus of the kidney, are able to produce large amounts of ROS via the NADPH oxidase. We previously demonstrated that integrin ␣1-null mice develop worse fibrosis than wild-type mice following glomerular injury and this is due, in part, to excessive ROS production by ␣1-null mesangial cells. In the present studies, we describe the mechanism whereby integrin ␣1-null mesangial cells produce excessive ROS. Integrin ␣1-null mesangial cells have constitutively increased basal levels of activated Rac1, which result in its increased translocation to the cell membrane, excessive ROS production, and consequent collagen IV deposition. Basal Rac1 activation is a direct consequence of ligand-independent increased epidermal growth factor receptor (EGFR) phosphorylation in ␣1-null mesangial cells. Thus, our study demonstrates that integrin ␣1␤1-EGFR cross talk is a key step in negatively regulating Rac1 activation, ROS production, and excessive collagen synthesis, which is a hallmark of diseases characterized by irreversible fibrosis.Integrin ␣1␤1, a major collagen binding receptor, is expressed in different cell types, including fibroblasts (45), endothelial cells (8), and mesangial cells in the glomerulus of the kidney (30, 53). Integrin ␣1␤1 confers the ability of cells to bind to collagenous substrata, including collagens I and IV (4, 45), and to proliferate on these substrata (45). Moreover, cells expressing integrin ␣1␤1 sense extracellular levels of collagen and downregulate its synthesis at both transcriptional and translational levels (4,14). Finally, we demonstrated that integrin ␣1␤1 also downregulates the production of reactive oxygen species (ROS) (4, 58).Following renal injury, mice lacking integrin ␣1␤1 develop more extensive glomerular fibrosis characterized by excessive accumulation of collagen type IV compared to wild-type (WT) mice (4, 58). Increased fibrosis is due to both a direct effect of the lack of integrin ␣1␤1-mediated downregulation of collagen IV synthesis and excessive ROS production by ␣1-null mesangial cells.Constitutive production of ROS by mesangial cells, a major cell type found in the glomerulus of the kidney, originates from an intrinsic NADPH oxidase (26, 48) that normally functions at a low level and increases in response to inflammatory stimuli, high glucose, or stress (25,34,35,37,55). The NADPH oxidase, highly characterized in phagocytes, is a multicomponent enzyme complex that consists of the membrane-bound cytochrome b 558 (p22 phox and gp91 phox ) and cytoplasmic proteins (p40 phox , p47 phox , p67 phox ) that translocate to the membrane following cellular stimulation to produce superoxide (3, 9, 47). A multicomponent phagocyte-like NADPH oxidase is also a major source of ROS in many nonphagocytic cells, including mesangial cells. In the phagocyte-like NADPH oxidase, the catalytic subunits are termed Nox proteins, with ...

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Negative regulation of EGFR signalling through integrin-α1β1-mediated activation of protein tyrosine phosphatase TCPTP

Cited by 185 publications

References 29 publications

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

Spermidine Stimulates T Cell Protein-tyrosine Phosphatase-mediated Protection of Intestinal Epithelial Barrier Function

Integrin α1β1 Controls Reactive Oxygen Species Synthesis by Negatively Regulating Epidermal Growth Factor Receptor-Mediated Rac Activation

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