MKP3 negatively modulates PDGF-induced Akt and Erk5 phosphorylation as well as chemotaxis

Razmara, Masoud; Eger, Glenda; Rorsman, Charlotte; Heldin, Carl‐Henrik; Lennartsson, Johan

doi:10.1016/j.cellsig.2011.11.001

Cited by 9 publications

(8 citation statements)

References 44 publications

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“…That being said, the possibility that Dusp6 dephosphorylates other targets than ERK1/2 cannot be totally excluded. For instance, Dusp6 has been shown to interact with other kinases such as CK2 (Hagan, Knutson, & Lange, 2013) and ERK5 (Razmara, Eger, Rorsman, Heldin, & Lennartsson, 2012;Sarközi et al, 2007). In this regard, ERK5 is particularly interesting since this MAPK can rescue intestinal epithelial turnover and tumor cell proliferation upon ERK1/2 inhibition (de Jong et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Dual‐specificity phosphatase 6 deletion protects the colonic epithelium against inflammation and promotes both proliferation and tumorigenesis

Beaudry

Langlois

Montagne

et al. 2018

Journal Cellular Physiology

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The Ras/mitogen‐activated protein kinase (MAPK) pathway controls fundamental cellular processes such as proliferation, differentiation, and apoptosis. The dual‐specificity phosphatase 6 (DUSP6) regulates cytoplasmic MAPK signaling by dephosphorylating and inactivating extracellular signal‐regulated kinase (ERK1/2) MAPK. To determine the role of DUSP6 in the maintenance of intestinal homeostasis, we characterized the intestinal epithelial phenotype of Dusp6 knockout (KO) mice under normal, oncogenic, and proinflammatory conditions. Our results show that loss of Dusp6 increased crypt depth and epithelial cell proliferation without altering colonic architecture. Crypt regeneration capacity was also enhanced, as revealed by ex vivo Dusp6 KO organoid cultures. Additionally, loss of Dusp6 induced goblet cell expansion without affecting enteroendocrine and absorptive cell differentiation. Our data also demonstrate that Dusp6 KO mice were protected from acute dextran sulfate sodium‐induced colitis, as opposed to wild‐type mice. In addition, Dusp6 gene deletion markedly enhanced tumor load in Apc Min/+ mice. Decreased DUSP6 expression by RNA interference in HT29 colorectal cancer cells enhanced ERK1/2 activation levels and promoted both anchorage‐independent growth in soft agar as well as invasion through Matrigel. Finally, DUSP6 mRNA expression in human colorectal tumors was decreased in advanced stage tumors compared with paired normal tissues. These results demonstrate that DUSP6 phosphatase, by controlling ERK1/2 activation, regulates colonic inflammatory responses, and protects the intestinal epithelium against oncogenic stress.

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Section: Discussionmentioning

confidence: 99%

Dual‐specificity phosphatase 6 deletion protects the colonic epithelium against inflammation and promotes both proliferation and tumorigenesis

Beaudry

Langlois

Montagne

et al. 2018

Journal Cellular Physiology

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“…NIH3T3 murine fibroblasts were a kind gift of Johan Lennartson (Razmara et al, ) and were cultured in Dulbecco's modified Eagle medium (DMEM) containing high glucose, 10% v/v fetal bovine serum and 100 U/mL penicillin/streptomycin (Sigma‐Aldrich). Cells were maintained in a humidified incubator at 37°C with 5% CO 2 and used for experiments between passages 6–12.…”

Section: Methodsmentioning

confidence: 99%

Commercially Available Preparations of Recombinant Wnt3a Contain Non‐Wnt Related Activities Which May Activate TGF‐β Signaling

Carthy

Engström

Heldin

et al. 2015

J of Cellular Biochemistry

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The Wnt ligands are a family of secreted signaling proteins which play key roles in a number of cellular processes under physiological and pathological conditions. Wnts bind to their membrane receptors and initiate a signaling cascade which leads to the nuclear localization and transcriptional activity of β-catenin. The development of purified recombinant Wnt ligands has greatly aided in our understanding of Wnt signaling and its functions in development and disease. In the current study, we identified non-Wnt related signaling activities which were present in commercially available preparations of recombinant Wnt3a. Specifically, we found that treatment of cultured fibroblasts with recombinant Wnt3a induced immediate activation of TGF-β and BMP signaling and this activity appeared to be independent of the Wnt ligand itself. Therefore, while purified recombinant Wnt ligands continue to be a useful tool for studying this signaling pathway, one must exercise a degree of caution when analyzing the results of experiments that utilize purified recombinant Wnt ligands.

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“…It is unlikely that ERK5 directly phosphorylates PKB/Akt, as it is well established that PKB/Akt is activated via phosphorylation of Thr308 in the activation loop via the mammalian target of rapamycin complex 2 (mTORC2) [40,41], as well as Ser473 in the C-terminus by phosphoinositide-dependent kinase-1 (PDK1) [42]. It may be that ERK5 regulates the activity of a phosphatase, such as protein phosphatase 2 (PP2A) [43] or MKP3 [44], which have been shown to regulate PKB/Akt dephosphorylation. The precise mechanism through which ERK5 regulates PKB/Akt phosphorylation and activation remains obscure.…”

Section: Erk5 and Endothelial Cell Physiology Inhibition Of Endothelimentioning

confidence: 99%

The role of ERK5 in endothelial cell function

Nithianandarajah-Jones

Wilm

Goldring

et al. 2014

Biochemical Society Transactions

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Extracellular-signal-regulated kinase 5 (ERK5), also termed big MAPK1 (BMK1), is the most recently discovered member of the mitogen-activated protein kinase (MAPK) family. It is expressed in a variety of tissues and is activated by a range of growth factors, cytokines and cellular stresses. Targeted deletion of Erk5 in mice has revealed that the ERK5 signalling cascade is critical for normal cardiovascular development and vascular integrity. In vitro studies have revealed that, in endothelial cells, ERK5 is required for preventing apoptosis, mediating shear-stress signalling and regulating tumour angiogenesis. The present review focuses on our current understanding of the role of ERK5 in regulating endothelial cell function.

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MKP3 negatively modulates PDGF-induced Akt and Erk5 phosphorylation as well as chemotaxis

Cited by 9 publications

References 44 publications

Dual‐specificity phosphatase 6 deletion protects the colonic epithelium against inflammation and promotes both proliferation and tumorigenesis

Dual‐specificity phosphatase 6 deletion protects the colonic epithelium against inflammation and promotes both proliferation and tumorigenesis

Commercially Available Preparations of Recombinant Wnt3a Contain Non‐Wnt Related Activities Which May Activate TGF‐β Signaling

The role of ERK5 in endothelial cell function

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