Cyclic AMP‐elevating agents induce the expression of MAP kinase phosphatase‐1 in PC12 cells

Burgun, Claude; Esteve, Laurent; Humblot, Nathalie; Aunis, Dominique; Zwiller, Jean

doi:10.1016/s0014-5793(00)02153-0

Cited by 41 publications

(30 citation statements)

References 32 publications

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“…In addition, this result could be explained through the reported activation of the MAP kinase phosphatases (MAPKPs) by PKA. 44 Our observation of an enhancement of ERK phosphorylation under the stimulus of orthovanadate, which cannot be neutralized by cAMP (data not shown), supports this proposal. Thus, we can speculate that in PDV cells, cAMP-activated PKA can block the ERK pathway by acting at 2 levels: modulating Raf-1 activity or activating MAPKPs.…”

Section: Discussionsupporting

confidence: 67%

Cyclic AMP inhibits TGFβ1‐induced cell‐scattering and invasiveness in murine‐transformed keratinocytes

Santibáñez

Olivares

Guerrero

et al. 2003

Intl Journal of Cancer

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Mouse-transformed keratinocytes cultured in the presence of transforming growth factor ␤1 (TGF-␤1) acquire an array of morphologic and functional properties that give rise to a migratory phenotype that expresses mesenchymal molecular markers. This cellular conversion involves activation of the Ras-ERK pathway, enhancement of urokinase (uPA) and matrix metalloproteinase-9 (MMP-9) expression and induction of invasiveness. In our present work, we demonstrate that cAMP and forskolin are able to prevent the expression of these mesenchymal properties, probably due to blockade of the Ras-ERK pathway. Our results also show that cAMP and forskolin are able to abolish the TGF-␤1-induced reorganization of the actin cytoskeleton that is characteristic of the mesenchymal phenotype and also inhibits the disruption of the E-cadherin cell to cell interactions. The latter responses seem to depend on the activity of protein kinase A, as demonstrated by the activation of the Ras-ERK pathway by specific protein kinase A inhibitors. © 2003 Wiley-Liss, Inc. Key words: cAMP; urokinase; matrix metalloproteinases; E-cadherin; epithelial-mesenchymal transdifferentiationPrevious reports have shown that in transformed keratinocytes transforming growth factor ␤1 (TGF-␤1) induces an epithelialmesenchymal transition (EMT) associated with the development of highly invasive and metastatic spindle cell carcinoma. 1 We also demonstrated that this conversion proceeds through the activation of the Ras-ERK pathway and involves enhancement of uPA and MMP-9 expression and induction of invasiveness. 2,3 The EMT is characterized by a set of transient phenotypic changes often associated with the acquisition of migratory properties by cancer cells and provides a means for cancer propagation through the organism. 4 The most conspicuous cellular EMT events can be grouped into the following categories: (i) cell scattering, which involves disruption of cell-cell association and further acquisition of cell motility; (ii) the production of tumoral matrixdegrading proteases; and (iii) remodeling of the actin cytoskeleton that provides the molecular framework for cellular motility. 5 Cell scattering is the only feature always present in EMT 6 and involves E-cadherin (E-cad) down-modulation. E-cad, a homotypic cell-tocell interaction molecule that is expressed in epithelial cells, can act as a tumor suppressor that contributes to preserving cellular architecture and polarization by its association with F-actin through ␣ and ␤ catenin. [7][8][9] It has been proposed that the second messenger cAMP can serve as an anticancer agent by acting as an inhibitor of the G1/S transition in the cell cycle or by inducing cell cycle-specific apoptosis. 10 -12 Moreover, recent data provide evidence that the modulation of intracellular cAMP levels can also regulate some cellular properties involved in cell motility. 13,14 At the signaling level, it has been demonstrated that an active cross-talk between the cAMP and the Ras-ERK signaling pathways allows cAMP to inhibit or activa...

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Section: Discussionsupporting

confidence: 67%

Cyclic AMP inhibits TGFβ1‐induced cell‐scattering and invasiveness in murine‐transformed keratinocytes

Santibáñez

Olivares

Guerrero

et al. 2003

Intl Journal of Cancer

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“…MKP-1 was the first phosphatase identified as an in vitro ERK-specific phosphatase (53)(54)(55). Further studies reveal that MKP-1 was ubiquitously induced by a wide variety of stimuli such as mitogens, hormones, oxidative-DNA damage cellular stresses, LPS, proinflammatory cytokines, and antiinflammatory agents (53,(55)(56)(57)(58). In addition, depending on the circumstances, MKP-1 dephosphorylates JNK and p38 (2,49,59).…”

Section: Discussionmentioning

confidence: 99%

Macrophage-Colony-Stimulating Factor-Induced Proliferation and Lipopolysaccharide-Dependent Activation of Macrophages Requires Raf-1 Phosphorylation to Induce Mitogen Kinase Phosphatase-1 Expression

Sánchez-Tilló

Comalada

Farrera

et al. 2006

The Journal of Immunology

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Macrophages are key regulators of immune responses. In the absence of an activating signal, murine bone marrow-derived macrophages undergo proliferation in response to their specific growth factor, namely M-CSF. The addition of bacterial LPS results in macrophage growth arrest and their engagement in a proinflammatory response. Although participation of ERKs is required for both macrophage proliferation and activation, ERK phosphorylation follows a more delayed pattern in response to activating agents. In primary macrophages, mitogen kinase phosphatase-1 (MKP-1) is a key regulator of the time course of MAPK activity. Here we showed that MKP-1 expression is dependent on Raf-1 activation. The time course of Raf-1 activation correlated with that of ERK-1/2. However, whereas ERK phosphorylation in response to M-CSF is Raf-1 dependent, in response to LPS, an alternative pathway directs the activation of these kinases. Inhibition of Raf-1 activity increased the expression of cyclin-dependent kinase inhibitors and growth arrest. In contrast, no effect was observed in the expression of proinflammatory cytokines and inducible NO synthase following LPS stimulation. The data reported here reveal new insights into how signaling determines opposing macrophage functions.

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“…Due to the nuclear localization of SF-1, which we have found to be dephosphorylated in response to cAMP (Sewer & Waterman 2002), we suspect that the DSP is an inducible nuclear enzyme. Interestingly, cAMP elevating agents such cAMP-dependent transcription requires a phosphatase · M B SEWER and M R WATERMAN 169 as forskolin and dbcAMP have been shown to induce the expression of MKP-1 (MAP kinase phosphatase-1; a nuclear DSP) in PC12 cells (Burgun et al 2000).…”

Section: Discussionmentioning

confidence: 99%

cAMP-dependent transcription of steroidogenic genes in the human adrenal cortex requires a dual-specificity phosphatase in addition to protein kinase A

Sewer¹,

Waterman²

2002

Journal of Molecular Endocrinology

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Steroid hormone biosynthesis in the adrenal cortex is controlled by the peptide hormone adrenocorticotropin (ACTH), which acts to increase intracellular cAMP and results in the activation of cAMP-dependent protein kinase A (PKA) and subsequent increase in steroidogenic gene transcription. Protein phosphorylation by PKA activates transcription of genes encoding steroidogenic enzymes; however the precise proteins which are phosphorylated remain to be determined. We have recently shown that phosphoprotein phosphatase (PP) activity is essential for cAMP-dependent transcription of the human CYP17 (hCYP17) gene in H295R adrenocortical cells. The aim of our current studies was to determine if inhibition of PP activity attenuates cAMP-dependent mRNA expression of other steroidogenic genes in H295R cells. Using various inhibitors of serine/threonine and tyrosine PPs, we examined the role of phosphatase activity on cAMP-dependent transcription of steroidogenic genes in the adrenal cortex. CYP11A, CYP11B1/2, CYP21, and adrenodoxin also require PP activity for cAMP-stimulated gene expression. Inhibition of both serine/threonine and tyrosine PP activities suppresses the cAMP-dependent mRNA expression of several steroidogenic genes, suggesting that a dual-specificity PP is essential for conveying ACTH/cAMP-stimulated transcription. We propose that PKA phosphorylates and activates a dual-specificity phosphatase, which mediates steroidogenic gene transcription in response to ACTH/cAMP.

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Cyclic AMP‐elevating agents induce the expression of MAP kinase phosphatase‐1 in PC12 cells

Cited by 41 publications

References 32 publications

Cyclic AMP inhibits TGFβ1‐induced cell‐scattering and invasiveness in murine‐transformed keratinocytes

Cyclic AMP inhibits TGFβ1‐induced cell‐scattering and invasiveness in murine‐transformed keratinocytes

Macrophage-Colony-Stimulating Factor-Induced Proliferation and Lipopolysaccharide-Dependent Activation of Macrophages Requires Raf-1 Phosphorylation to Induce Mitogen Kinase Phosphatase-1 Expression

cAMP-dependent transcription of steroidogenic genes in the human adrenal cortex requires a dual-specificity phosphatase in addition to protein kinase A

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