Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells

Noordman, Yvet E.; Jansen, Patrick A.; Hendriks, Wiljan

doi:10.1186/1750-2187-1-4

Cited by 18 publications

(16 citation statements)

References 34 publications

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“…MKPs are well-known phosphatases that specifically dephosphorylate pTpYERK through a posttranscriptional negative feedback mechanism [24], [27], which would be involved in halting ERK-induced cellular events. A protein-tyrosine phosphatase (PTP) acts as an important regulator of ERK in hematopoietic cells [28], although PTPs are dispensable for ERK regulation in other cells [29]. On the other hand, accumulating evidence indicates that PP2A has complex inhibitory and stimulatory effects on growth factor- and/or adhesion-induced signalling, in particular the ERK cascade.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Regulation of Extracellular Signal-Regulated Kinase (ERK) by Protein Phosphatase 2A Regulatory Subunit B56γ1 in Nuclei Induces Cell Migration

et al. 2013

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Extracellular signal-regulated kinase (ERK) signalling plays a central role in various biological processes, including cell migration, but it remains unknown what factors directly regulate the strength and duration of ERK activation. We found that, among the B56 family of protein phosphatase 2A (PP2A) regulatory subunits, B56γ1 suppressed EGF-induced cell migration on collagen, bound to phosphorylated-ERK, and dephosphorylated ERK, whereas B56α1 and B56β1 did not. B56γ1 was immunolocalized in nuclei. The IER3 protein was immediately highly expressed in response to costimulation of cells with EGF and collagen. Knockdown of IER3 inhibited cell migration and enhanced dephosphorylation of ERK. Analysis of the time course of PP2A-B56γ1 activity following the costimulation showed an immediate loss of phosphatase activity, followed by a rapid increase in activity, and this activity then remained at a stable level that was lower than the original level. Our results indicate that the strength and duration of the nuclear ERK activation signal that is initially induced by ERK kinase (MEK) are determined at least in part by modulation of the phosphatase activity of PP2A-B56γ1 through two independent pathways.

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Section: Introductionmentioning

confidence: 99%

Dynamic Regulation of Extracellular Signal-Regulated Kinase (ERK) by Protein Phosphatase 2A Regulatory Subunit B56γ1 in Nuclei Induces Cell Migration

et al. 2013

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“…PTPRR dephosphorylates p44/42 MAPK in response to some growth factors in cell lines. 24,43,44 Molecules that inhibit the MAPK signaling, such as nonmetastatic 23, Raf kinase inhibitor protein, mitogen-activated protein kinase kinase 4 and mitogen-activated protein kinase kinase 6, inhibit metastasis. 45,46 We characterized the tumor-suppressor function of PTPRR, especially its role in metastasis via the MAPK pathway, in a cervical cancer model.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer

Lin

Huang

et al. 2012

Oncogene

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Epigenetic modifications are a driving force in carcinogenesis. However, their role in cancer metastasis remains poorly understood. The present study investigated the role of DNA methylation in the cervical cancer metastasis. Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the inhibition of metastasis by DNMT3B interference. Using methyl-DNA immunoprecipitation coupled with microarray analysis, we found that the protein tyrosine phosphatase receptor type R (PTPRR) was silenced through DNMT3B-mediated methylation in the cervical cancer. PTPRR inhibited p44/42 MAPK signaling, the expression of the transcription factor AP1, human papillomavirus (HPV) oncogenes E6/E7 and DNMTs. The methylation status of PTPRR increased in cervical scrapings (n=358) in accordance with disease severity, especially in invasive cancer. Methylation of the PTPRR promoter has an important role in the metastasis and may be a biomarker of invasive cervical cancer.

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“…Often, the subcellular localization of the signal target is the same, but the distinct signals elicit very different outcomes. The best studied of this phenomenon is the PC-12 model system (1)(2)(3). PC-12 cells are rat-derived neural progenitor cells that can be induced to proliferate upon epidermal growth factor (EGF) stimulation, or to differentiate upon neural growth factor (NGF) stimulation (3).…”

Section: Introductionmentioning

confidence: 99%

Specificity and Robustness of the Mammalian MAPK-IEG Network

Thalhauser

Komarova

2009

Biophysical Journal

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The mitogen-activated protein kinase cascade is a conserved signal transduction pathway found in organisms of complexity spanning from yeast to humans. In many mammalian tissue types, this pathway can correctly transduce signals from different extracellular messengers, leading to specific and often mutually exclusive cellular responses. The transduced signal is tuned by a complicated set of positive and negative feedback control mechanisms and fed into a downstream gene expression network. This network, based on the immediate early gene system, has two possible, mutually exclusive outcomes. Using a mathematical model, we study how different stimuli lead to different temporal signal structure. Further, we investigate how each of the feedback controls contributes to the overall specificity of the gene expression output, and hypothesize that the complicated nature of the mammalian mitogen-activated protein kinase pathway results in a system able to robustly identify and transduce the proper signal without investing in two completely separate signal cascades. Finally, we quantify the role of the RKIP protein in shaping the signal, and propose a novel mechanism of its involvement in cancer metastasis.

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Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells

Cited by 18 publications

References 34 publications

Dynamic Regulation of Extracellular Signal-Regulated Kinase (ERK) by Protein Phosphatase 2A Regulatory Subunit B56γ1 in Nuclei Induces Cell Migration

Dynamic Regulation of Extracellular Signal-Regulated Kinase (ERK) by Protein Phosphatase 2A Regulatory Subunit B56γ1 in Nuclei Induces Cell Migration

Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer

Specificity and Robustness of the Mammalian MAPK-IEG Network

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