Role of MEKK2-MEK5 in the regulation of TNF-α gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells

Chayama, Kazuaki; Papst, Philip J.; Garrington, Timothy P.; Pratt, Joanne C.; Ishizuka, Tamotsu; Webb, Saiphone; Ganiatsas, Soula; Zon, Leonard I.; Sun, Weiyong; Johnson, Gary L.; Gelfand, Erwin W.

doi:10.1073/pnas.081021898

Cited by 70 publications

(72 citation statements)

References 36 publications

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“…HBx activates AP-1 via a pathway that is mediated by the activation of ERK and JNK [21,35] . AP-1 and JNK are downstream effectors of MEKK2 [15,16,19] . To further validate that HBx upregulated MEKK2, we examined the activation of AP-1 and JNK by silencing the expression of HBx or MEKK2 in HepG2.2.15 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, the luciferase reporter gene assay showed that HBx RNAi abolished the enhancement of MEKK2 promoter activity in HepG2-X/H7402-X/HepG2.2.15 cells in a dose-dependent manner ( Figure 2E). It has been reported that MEKK2 is involved in the activation of AP-1 and JNK [15,16,19] . To further confirm the HBxmediated regulation of MEKK2, we examined the downstream effectors of MEKK2, such as AP-1 and JNK, in HepG2.2.15 cells.…”

Section: Wwwnaturecom/aps Kong Gy Et Almentioning

confidence: 99%

“…In response to different external stimuli, these MAPKs are activated via a module that uses a MAPKKK-MAPKK-MAPK pathway. Mitogen-activated protein kinase kinase kinase 2 (MEKK2), which is a member of the MAPK signaling pathway, activates JNK and ERK5 [15,16] . MEKK2 knockout mouse studies have identified important functions for MEKK2 in the T-cell receptor, epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2) signaling pathways [15,17,18] .…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis B virus X protein promotes hepatoma cell proliferation via upregulation of MEKK2

Kong

Zhang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the mechanism underlying the increase of hepatoma cell proliferation by hepatitis B virus X protein (HBx). Methods: HepG2, H7402 and HepG2.2.15 cells, which constitutively replicated hepatitis B virus were used. The effects of HBx on hepatoma cell proliferation were examined using 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and MTT assay. The expression level of MEKK2 was measured using RT-PCR, Western blot and luciferase reporter gene assay. The activity of activator protein 1 (AP-1) was detected using luciferase reporter gene assay. The phosphorylation levels of JNK and c-Jun were measured using Western blot. The expression levels of HBx and MEKK2 in 11 clinical hepatocellular carcinoma (HCC) tissues were measured using real time PCR and Western blot. In addition, the expression of MEKK2 in 95 clinical HCC tissues was examined using immunohistochemistry. Results: HBx significantly enhanced HepG2-X cell proliferation. In HepG2-X, H7402-X and HepG2.2.15 cells, the expression level of MEKK2 was remarkably increased. In HepG2.2.15 cells, HBx was found to activate JNK and AP-1, which were the downstream effectors of MEKK2 in HepG2-X and HepG2.2.15 cells. In 11 clinical HCC tissues, both HBx and MEKK2 expression levels were remarkably increased, as compared to those in the corresponding peritumor tissues. In 95 clinical HCC tissues, the rate of detection of MEKK2 was 85.3%. Conclusion: HBx promotes hepatoma cell proliferation via upregulating MEKK2, which may be involved in hepatocarcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Wwwnaturecom/aps Kong Gy Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatitis B virus X protein promotes hepatoma cell proliferation via upregulation of MEKK2

Kong

Zhang

et al. 2011

Acta Pharmacol Sin

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“…4; Chayama et al, 2001;Hammaker et al, 2004;Kesavan et al, 2004). MEKK2 knockout mice are viable and fertile without any apparent developmental malformations.…”

Section: Mekk2 (Omim#*609487)mentioning

confidence: 99%

MAP3Ks as central regulators of cell fate during development

Craig

Stevens

Vaillancourt

et al. 2008

Developmental Dynamics

112

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“…Some reports demonstrated that MEK5 was regulated by TNFa/JNK signal pathway (Dent et al, 2003;Yoshizumi et al, 2003). MEKK2 and MEKK3 have been demonstrated as MEK5/ERK5 direct upstream regulators (Chao et al, 1999;Chayama et al, 2001;Sun et al, 2001). It has been proven that MEK5 acts through regulating MEF2C, a member of the MEF2 transcription factor family (Kato et al, 1997).…”

Section: Introductionmentioning

confidence: 99%