Deletion of
            Ptpn11
            (Shp2) in Cardiomyocytes Causes Dilated Cardiomyopathy via Effects on the Extracellular Signal–Regulated Kinase/Mitogen-Activated Protein Kinase and RhoA Signaling Pathways

ABSTRACT Diseases associated with Chlamydia infection, such as pelvic inflammatory disease and ectopic pregnancy, are due to inflammation-mediated tissue damage and scarring that occur after chronic or repeated infections. The inflammatory chemokine interleukin-8 (IL-8) is produced by Chlamydia-infected cells through an endogenous mechanism of activation, independent of soluble factors in the supernatant. The host signaling pathways necessary for this response are not understood, but the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) has been shown to be activated at similar times as IL-8 mRNA up-regulation. The purpose of this study was to elucidate the MAPK pathways necessary to induce the endogenous IL-8 response to Chlamydia trachomatis infection of epithelial cells. IL-8 induced by infection with C. trachomatis L2 was shown to be dependent on ERK and independent of p38 and Jun N-terminal MAPK by use of chemical inhibitors of the signaling pathways. Persistent ERK activation during IL-8 mRNA production at 24 h postinfection was necessary to maintain the response. C. trachomatis serovar D also induced IL-8 in an ERK-dependent manner. We concluded that IL-8 induced during infection of epithelial cells is dependent on continual activation of ERK by C. trachomatis.

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Faculty Opinions recommendation of Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1006218.77810 ◽

2002 ◽

Author(s):

Angel Nebreda

Keyword(s):

Protein Kinase ◽

Mitogen Activated Protein Kinase ◽

Premature Senescence ◽

Extracellular Signal Regulated Kinase ◽

Oncogenic Ras ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Sequential Activation

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TRAF6-Dependent Mitogen-Activated Protein Kinase Activation Differentially Regulates the Production of Interleukin-12 by Macrophages in Response to Toxoplasma gondii

Infection and Immunity ◽

10.1128/iai.72.10.5662-5667.2004 ◽

2004 ◽

Vol 72 (10) ◽

pp. 5662-5667 ◽

Cited By ~ 43

Author(s):

Nicola J. Mason ◽

Jim Fiore ◽

Takashi Kobayashi ◽

Katherine S. Masek ◽

Yongwon Choi ◽

...

Keyword(s):

Protein Kinase ◽

Toxoplasma Gondii ◽

Signaling Pathways ◽

Intracellular Signaling ◽

Mitogen Activated Protein Kinase ◽

Interleukin 12 ◽

Wild Type ◽

Kinase Activation ◽

Extracellular Signal ◽

Mitogen Activated Protein

ABSTRACT The production of interleukin-12 (IL-12) is critical to the development of innate and adaptive immune responses required for the control of intracellular pathogens. Many microbial products signal through Toll-like receptors (TLR) and activate NF-κB family members that are required for the production of IL-12. Recent studies suggest that components of the TLR pathway are required for the production of IL-12 in response to the parasite Toxoplasma gondii; however, the production of IL-12 in response to this parasite is independent of NF-κB activation. The adaptor molecule TRAF6 is involved in TLR signaling pathways and associates with serine/threonine kinases involved in the activation of both NF-κB and mitogen-activated protein kinase (MAPK). To elucidate the intracellular signaling pathways involved in the production of IL-12 in response to soluble toxoplasma antigen (STAg), wild-type and TRAF6−/− mice were inoculated with STAg, and the production of IL-12(p40) was determined. TRAF6−/− mice failed to produce IL-12(p40) in response to STAg, and TRAF6−/− macrophages stimulated with STAg also failed to produce IL-12(p40). Studies using Western blot analysis of wild-type and TRAF6−/− macrophages revealed that stimulation with STAg resulted in the rapid TRAF6-dependent phosphorylation of p38 and extracellular signal-related kinase, which differentially regulated the production of IL-12(p40). The studies presented here demonstrate for the first time that the production of IL-12(p40) in response to toxoplasma is dependent upon TRAF6 and p38 MAPK.

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Big Mitogen-Activated Protein Kinase 1 (BMK1)/Extracellular Signal Regulated Kinase 5 (ERK5) Is Involved in Platelet-Derived Growth Factor (PDGF)-Induced Vascular Smooth Muscle Cell Migration

Hypertension Research ◽

10.1291/hypres.30.1107 ◽

2007 ◽

Vol 30 (11) ◽

pp. 1107-1117 ◽

Cited By ~ 23

Author(s):

Yuki IZAWA ◽

Masanori YOSHIZUMI ◽

Keisuke ISHIZAWA ◽

Yoshiko FUJITA ◽

Shuji KONDO ◽

...

Keyword(s):

Smooth Muscle ◽

Cell Migration ◽

Growth Factor ◽

Protein Kinase ◽

Mitogen Activated Protein Kinase ◽

Platelet Derived Growth Factor ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Smooth Muscle Cell Migration ◽

Mitogen Activated Protein

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Cooperation of p38 and Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase Pathways during Granulocyte Colony-stimulating Factor-induced Hemopoietic Cell Proliferation

Journal of Biological Chemistry ◽

10.1074/jbc.274.7.4096 ◽

1999 ◽

Vol 274 (7) ◽

pp. 4096-4105 ◽

Cited By ~ 80

Author(s):

Oliver Rausch ◽

Christopher J. Marshall

Keyword(s):

Cell Proliferation ◽

Protein Kinase ◽

Mitogen Activated Protein Kinase ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Hemopoietic Cell ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Stimulating Factor

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The Insulin Receptor: A Potential Target of Amarogentin Isolated from Gentiana rigescens Franch That Induces Neurogenesis in PC12 Cells

Biomedicines ◽

10.3390/biomedicines9050581 ◽

2021 ◽

Vol 9 (5) ◽

pp. 581

Author(s):

Lihong Cheng ◽

Hiroyuki Osada ◽

Tianyan Xing ◽

Minoru Yoshida ◽

Lan Xiang ◽

...

Keyword(s):

Protein Kinase ◽

Insulin Receptor ◽

Signaling Pathways ◽

Neurite Outgrowth ◽

Pc12 Cells ◽

Mitogen Activated Protein Kinase ◽

Potential Target ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Gentiana Rigescens

Amarogentin (AMA) is a secoiridoid glycoside isolated from the traditional Chinese medicine, Gentiana rigescens Franch. AMA exhibits nerve growth factor (NGF)-mimicking and NGF-enhancing activities in PC12 cells and in primary cortical neuron cells. In this study, a possible mechanism was found showing the remarkable induction of phosphorylation of the insulin receptor (INSR) and protein kinase B (AKT). The potential target of AMA was predicted by using a small-interfering RNA (siRNA) and the cellular thermal shift assay (CETSA). The AMA-induced neurite outgrowth was reduced by the siRNA against the INSR and the results of the CETSA suggested that the INSR showed a significant thermal stability-shifted effect upon AMA treatment. Other neurotrophic signaling pathways in PC12 cells were investigated using specific inhibitors, Western blotting and PC12(rasN17) and PC12(mtGAP) mutants. The inhibitors of the glucocorticoid receptor (GR), phospholipase C (PLC) and protein kinase C (PKC), Ras, Raf and mitogen-activated protein kinase (MEK) significantly reduced the neurite outgrowth induced by AMA in PC12 cells. Furthermore, the phosphorylation reactions of GR, PLC, PKC and an extracellular signal-regulated kinase (ERK) were significantly increased after inducing AMA and markedly decreased after treatment with the corresponding inhibitors. Collectively, these results suggested that AMA-induced neuritogenic activity in PC12 cells potentially depended on targeting the INSR and activating the downstream Ras/Raf/ERK and PI3K/AKT signaling pathways. In addition, the GR/PLC/PKC signaling pathway was found to be involved in the neurogenesis effect of AMA.

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