Phosphorylated extracellular signal-regulated kinase 1/2 immunoreactivity and its protein levels in the gerbil hippocampus during normal aging

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

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Adenovirus-Induced Extracellular Signal-Regulated Kinase Phosphorylation during the Late Phase of Infection Enhances Viral Protein Levels and Virus Progeny

Cancer Research ◽

10.1158/0008-5472.can-05-1484 ◽

2006 ◽

Vol 66 (3) ◽

pp. 1282-1288 ◽

Cited By ~ 31

Author(s):

Michael Schümann ◽

Matthias Dobbelstein

Keyword(s):

Viral Protein ◽

Late Phase ◽

Extracellular Signal Regulated Kinase ◽

Protein Levels ◽

Extracellular Signal ◽

Virus Progeny ◽

Kinase Phosphorylation

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SINO Syndrome Causative KIDINS220/ARMS Gene Regulates Adipocyte Differentiation

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.619475 ◽

2021 ◽

Vol 9 ◽

Author(s):

Kaihui Zhang ◽

Wenxing Sun ◽

Yi Liu ◽

Yuqiang Lv ◽

Daisen Hou ◽

...

Keyword(s):

Adipocyte Differentiation ◽

Pathogenic Mutation ◽

Chinese Family ◽

Extracellular Signal Regulated Kinase ◽

Protein Levels ◽

Cell Dysfunction ◽

Whole Exome ◽

Extracellular Signal ◽

Negative Role ◽

Chromosome Microarray

Nonsense variants in KIDINS220/ARMS were identified as the main cause of spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome, a rare disease with birth defects in brachycephaly, neurological disorder, and obesity. The cause of neural cell dysfunction by KIDINS220/ARMS were extensively studied while the cause of obesity in SINO syndrome remains elusive. Here, we identified KIDINS220/ARMS as an adipocyte differentiation-regulating gene. A Chinese family, mother and her two sons, all showed severe symptoms of SINO syndrome. G-banding karyotyping, chromosome microarray analysis, and whole exome sequencing revealed a novel amber mutation, c.3934G>T (p. E1312X), which was close to the C-terminal region of KIDINS220/ARMS and resulted in the premature of the protein. Both the mRNA and protein levels of KIDINS220/ARMS gradually decreased during adipocyte differentiation. Knockdown of KINDINS220/ARMS could prompt adipocyte differentiation and lipid accumulation while overexpression of KIDINS220/ARMS decrease the rate of matured adipocytes. Furthermore, we demonstrated that KIDINS220/ARMS inhibits adipocyte maturation through sustained extracellular signal-regulated kinase signaling. In conclusion, this is the first report about a vertical heredity of severe dominant pathogenic mutation of KIDINS220/ARMS, suggested that KIDINS220/ARMS played a negative role in adipocyte maturation, explained the cause of obesity in SINO syndrome and could highlight the importance of adipocyte differentiation in neuron functions.

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Regulation of c-Raf Stability through the CTLH Complex

International Journal of Molecular Sciences ◽

10.3390/ijms20040934 ◽

2019 ◽

Vol 20 (4) ◽

pp. 934 ◽

Cited By ~ 2

Author(s):

Christina McTavish ◽

Wesley Bérubé-Janzen ◽

Xu Wang ◽

Matthew Maitland ◽

Louisa Salemi ◽

...

Keyword(s):

Cell Transformation ◽

Direct Interaction ◽

Central Component ◽

Extracellular Signal Regulated Kinase ◽

Protein Levels ◽

Extracellular Signal ◽

Ubiquitin Ligase Complex ◽

Tumour Formation ◽

Cancer Types ◽

Novel Target

c-Raf is a central component of the extracellular signal-regulated kinase (ERK) pathway which is implicated in the development of many cancer types. RanBPM (Ran-Binding Protein M) was previously shown to inhibit c-Raf expression, but how this is achieved remains unclear. RanBPM is part of a recently identified E3 ubiquitin ligase complex, the CTLH (C-terminal to LisH) complex. Here, we show that the CTLH complex regulates c-Raf expression through a control of its degradation. Several domains of RanBPM were found necessary to regulate c-Raf levels, but only the C-terminal CRA (CT11-RanBPM) domain showed direct interaction with c-Raf. c-Raf ubiquitination and degradation is promoted by the CTLH complex. Furthermore, A-Raf and B-Raf protein levels are also regulated by the CTLH complex, indicating a common regulation of Raf family members. Finally, depletion of CTLH subunits RMND5A (required for meiotic nuclear division 5A) and RanBPM resulted in enhanced proliferation and loss of RanBPM promoted tumour growth in a mouse model. This study uncovers a new mode of control of c-Raf expression through regulation of its degradation by the CTLH complex. These findings also uncover a novel target of the CTLH complex, and suggest that the CTLH complex has activities that suppress cell transformation and tumour formation.

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Osteopontin Induced Vascular Endothelial Growth Factor Production in Dispersed Nasal Polyp Cells through the Phosphatidylinositol 3-Kinase–Protein Kinase B and the Extracellular Signal-Regulated Kinase 1/2 Pathways

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2017.31.4449 ◽

2017 ◽

Vol 31 (4) ◽

pp. e35-e41 ◽

Cited By ~ 2

Author(s):

Jingdong Du ◽

Huadong Mao ◽

Hong Ouyang ◽

Yan Xin

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Protein Kinase B ◽

Vascular Endothelial ◽

Phosphatidylinositol 3 Kinase ◽

Extracellular Signal Regulated Kinase ◽

Protein Levels ◽

Extracellular Signal ◽

Endothelial Growth Factor ◽

Normal Controls

Background Osteopontin (OPN) is involved in cell survival, migration, and angiogenesis. The role of OPN in inducing angiogenesis in tumor has been confirmed. In this study, we investigated the expression of OPN in patients with chronic rhinosinusitis (CRS) with nasal polyp (NP) and the relationship of OPN with vascular endothelial growth factor (VEGF) production. Methods We enrolled 45 subjects with CRS (25 with CRS with NPs [CRSwNP] and 20 subjects with CRS without NPs [CRSsNP]), and with 14 normal controls to determine the expression of OPN and VEGF. The distribution, messenger RNA (mRNA), and protein levels of OPN and VEGF were examined by immunohistochemistry, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. The effect of OPN on the VEGF production was tested in dispersed NP cells (DNPC) and the involved signaling pathways were examined by Western blot. Results In NP tissue of the subjects with CRSwNP, the epithelial cells, interstitial cells, glandular cells, and endothelial cells were positive for OPN and VEGF staining, whereas OPN and VEGF immunoactivity in specimens of subjects with CRSsNP and in normal controls was significantly reduced. We found that the immunostainings, the mRNA expression, and the protein levels of OPN and VEGF were significantly increased in NPs compared with normal controls. OPN induced VEGF production by DNPCs in a time- and dose-dependent manner through phosphatidylinositol 3-kinase- protein kinase B and the extracellular signal-regulated kinase 1/2 pathway. Moreover, VEGF also induced OPN production, which formed a positive feedback between OPN and VEGF. Conclusion Our findings demonstrated that OPN and VEGF were overproduced in NPs and that OPN induced VEGF production, which indicated that OPN-VEGF axis might contribute to angiogenesis in NPs.

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