scholarly journals Role of p90RSK in regulating the Crabtree effect: implications for cancer

2013 ◽  
Vol 41 (1) ◽  
pp. 124-126 ◽  
Author(s):  
Emily K. Redman ◽  
Paul S. Brookes ◽  
Marcin K. Karcz
Keyword(s):  
Cancer Cell ◽  
High Glucose ◽  
Cell Metabolism ◽  
Cell Signalling ◽  
Cell Types ◽  
Crabtree Effect ◽  
Glucose Levels ◽  
Mitogen Activated Protein ◽  
Ribosomal S6 Kinase

High glucose inhibits mitochondrial respiration, known as the ‘Crabtree effect’, in cancer cells and possibly other cell types. The upstream pathways regulating this phenomenon are poorly understood. In diabetes, where glucose levels are elevated, the p90RSK (p90 ribosomal S6 kinase) has received much attention as a potential upstream mediator of the effects of high glucose. Evidence is also emerging that p90RSK may play a role in cancer cell signalling, although the role of p90RSK in regulating cancer cell metabolism is unclear. In the present paper, we provide an overview of the Crabtree effect and its relationship to mitochondrial metabolism. Furthermore, preliminary data are presented suggesting a role for p90RSK and its upstream components, the ERK (extracellular-signal-regulated kinase) family of MAPKs (mitogen-activated protein kinases), in the Crabtree effect.

scholarly journals Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

2021 ◽  
Vol 43 (2) ◽  
pp. 767-781
Author(s):  
Vanessa Pinatto Gaspar ◽  
Anelise Cardoso Ramos ◽  
Philippe Cloutier ◽  
José Renato Pattaro Junior ◽  
Francisco Ferreira Duarte Junior ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Interactions ◽  
Ribosome Biogenesis ◽  
Cell Metabolism ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Cellular Mechanisms ◽  
Cancerous Cell ◽  
First Time

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

scholarly journals p38α Mitogen-activated Protein Kinase Sensitizes Cells to Apoptosis Induced by Different Stimuli

2004 ◽  
Vol 15 (2) ◽  
pp. 922-933 ◽  
Author(s):  
Almudena Porras ◽  
Susana Zuluaga ◽  
Emma Black ◽  
Amparo Valladares ◽  
Alberto M. Alvarez ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Survival Pathways ◽  
Proapoptotic Protein ◽  
Extracellular Signal ◽  
Survival Pathway ◽  
Mitogen Activated Protein

p38α mitogen-activated protein (MAP) kinase is a broadly expressed signaling molecule that participates in the regulation of cellular responses to stress as well as in the control of proliferation and survival of many cell types. We have used cell lines derived from p38α knockout mice to study the role of this signaling pathway in the regulation of apoptosis. Here, we show that cardiomyocytes and fibroblasts lacking p38α are more resistant to apoptosis induced by different stimuli. The reduced apoptosis of p38α-deficient cells correlates with decreased expression of the mitochondrial proapoptotic protein Bax and the apoptosis-inducing receptor Fas/CD-95. Cells lacking p38α also have increased extracellular signal-regulated kinase (ERKs) MAP kinase activity, and the up-regulation of this survival pathway seems to be at least partially responsible for the reduced levels of apoptosis in the absence of p38α. Phosphorylation of the transcription factor STAT3 on Ser-727, mediated by the extracellular signal-regulated kinase MAP kinase pathway, may contribute to the decrease in both Bax and Fas expression in p38α-/- cells. Thus, p38α seems to sensitize cells to apoptosis via both up-regulation of proapoptotic proteins and down-regulation of survival pathways.

scholarly journals Mitogen Kinase Kinase (MKK7) controls cytokine production in vitro and in vivo in mice

2021 ◽  
Author(s):  
Amada D. Caliz ◽  
Hyung-Jin Yoo ◽  
Anastassiia Vertii ◽  
Cathy Tournier ◽  
Roger J. Davis ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Cell Types ◽  
Minor Role ◽  
Cellular Processes ◽  
Mitogen Activated Protein ◽  
And Migration ◽  
Jnk Activation

Mitogen kinase kinase 4 (MKK4) and Mitogen kinase kinase 7 (MKK7) are members of the MAP2K family which can activate downstream mitogen-activated protein kinases (MAPKs). MKK4 has been implicated in the activation of both, c-Jun N-terminal Kinase (JNK) and p38 MAPK, whereas MKK7 only activates JNK in response to different stimuli. The stimuli as well as cell type determine the choice of MAP2K member that mediates the response. In a variety of cell types, the MKK7 contributes to the activation of downstream MAPKs, JNK, which is known to regulate essential cellular processes, such as cell death, differentiation, stress response, and cytokine secretion. Previous studies have implicated the role of MKK7 in stress signaling pathways and cytokine production. However, little is known about the degree to which MKK7 and MKK4 contributes to innate immune response in macrophages as well as during inflammation in vivo. To address this question and elucidate the role of MKK7 and MKK4 in macrophage and in vivo, we developed MKK7- and MKK4-deficient mouse models with tamoxifen-inducible Rosa26 CreERT. This study reports that MKK7 is required for JNK activation both in vitro and in vivo. Additionally, we demonstrated that MKK7 in macrophages is necessary for LPS induced cytokine production and migration which appears to be a major contributor to the inflammatory response in vivo. Whereas MKK4 plays a significant but minor role in cytokine production in vivo.

scholarly journals Gene expression of epithelial glucose transporters: the role of diabetes mellitus.

1994 ◽  
Vol 5 (5) ◽  
pp. S29
Author(s):  
J H Dominguez ◽  
B Song ◽  
L Maianu ◽  
W T Garvey ◽  
M Qulali
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Small Intestine ◽  
High Glucose ◽  
Glucose Transporter ◽  
Basolateral Membrane ◽  
Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Extracellular Level

The functions of absorption of dietary glucose by the small intestine and reabsorption of filtered glucose by the renal proximal tubule are strikingly similar in their organization and in the way they adapt to uncontrolled diabetes mellitus. In both cases, transepithelial glucose and Na+ fluxes are augmented. The epithelial adaptations to hyperglycemia of uncontrolled diabetes are accomplished by increasing the glucose transport surface area and the number of the efflux glucose transporter GLUT2 located in the basolateral membrane. The signals that modify the size of the epithelium and the overexpression of basolateral GLUT2 are not known. It was speculated that high glucose levels and enhanced Na+ flux may be important factors in the signaling event that culminates in a renal and intestinal epithelium that is modified to transport higher rates of glucose against a higher extracellular level of glucose.

scholarly journals How treatments with endocrine and metabolic drugs influence pituitary cell function

2020 ◽  
Vol 9 (2) ◽  
pp. R14-R27 ◽  
Author(s):  
Giovanni Tulipano
Keyword(s):  
Protein Kinase ◽  
Mammalian Cells ◽  
Cell Function ◽  
Cell Metabolism ◽  
Cell Signalling ◽  
Pituitary Cell ◽  
Pituitary Cells ◽  
Transduction Mechanisms ◽  
Amp Activated Protein Kinase

A variety of endocrine and metabolic signals regulate pituitary cell function acting through the hypothalamus-pituitary neuroendocrine axes or directly at the pituitary level. The underlying intracellular transduction mechanisms in pituitary cells are still debated. AMP-activated protein kinase (AMPK) functions as a cellular sensor of low energy stores in all mammalian cells and promotes adaptive changes in response to calorie restriction. It is also regarded as a target for therapy of proliferative disorders. Various hormones and drugs can promote tissue-specific activation or inhibition of AMPK by enhancing or inhibiting AMPK phosphorylation, respectively. This review explores the preclinical studies published in the last decade that investigate the role of AMP-activated protein kinase in the intracellular transduction pathways downstream of endocrine and metabolic signals or drugs affecting pituitary cell function, and its role as a target for drug therapy of pituitary proliferative disorders. The effects of the hypoglycemic agent metformin, which is an indirect AMPK activator, are discussed. The multiple effects of metformin on cell metabolism and cell signalling and ultimately on cell function may be either dependent or independent of AMPK. The in vitro effects of metformin may also help highlighting differences in metabolic requirements between pituitary adenomatous cells and normal cells.

scholarly journals Hyperglycemia Acutely Increases Monocyte Extracellular Signal-Regulated Kinase Activity in Vivo in Humans

2001 ◽  
Vol 86 (3) ◽  
pp. 1301-1305 ◽  
Author(s):  
Giulio Ceolotto ◽  
Alessandra Gallo ◽  
Michelangelo Sartori ◽  
Roberto Valente ◽  
Elisabetta Baritono ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Mitogen Activated Protein Kinase ◽  
Glucose Levels ◽  
Extracellular Signal ◽  
Patients With Diabetes ◽  
Mitogen Activated Protein ◽  
Negative Role ◽  
Long Term Prognosis

Glycemic spikes may negatively affect the long-term prognosis of patients with diabetes. Extracellular signal-regulated kinases (ERKs) are intracellular mediators of cell proliferation, and they can be activated in response to high glucose levels. However, the modifications of their activity in response to hyperglycemia have been poorly investigated, in vivo, in humans. Thus, we sought to determine in circulating monocytes: 1) the role of hyperglycemia in ERKs activity and phosphorylation, and 2) whether hyperglycemia affects mitogen-activated protein kinase kinase (MEK) activity and mitogen-activated protein phosphatase-1 (MKP-1) expression. These goals were performed in five normal subjects. Baseline monocyte ERKs activity was 60 ± 5 pmol/min·mg protein; when exogenous hyperglycemia was induced, both monocyte ERKs activity (81 ± 11 pmol/min·mg protein; P < 0.05) and phosphorylation significantly increased (P < 0.01). MEK activity was significantly increased by hyperglycemia (1251 ± 136 vs. 2000 ± 42 cpm; P = 0.0017), whereas no changes were observed in MKP-1 expression. We conclude that hyperglycemia acutely stimulates ERKs activity and phosphorylation in human monocytes by the MEK pathway in vivo. These findings may be relevant in understanding the negative role of acute hyperglycemia on monocyte pathophysiology.

Signalling during epidermal development

2007 ◽  
Vol 35 (1) ◽  
pp. 156-160 ◽  
Author(s):  
G.C. Ingram
Keyword(s):  
Cell Signalling ◽  
Cell Types ◽  
Cellular Level ◽  
In Planta ◽  
Future Directions ◽  
Signalling Molecules ◽  
Physical Accessibility ◽  
Epidermal Development ◽  
Cell Cell

The process of L1 specification early in plant embryogenesis, and subsequent maintenance and elaboration of epidermal organization, are fundamental to plant growth and fitness. To occur in a co-ordinated fashion, these processes require considerable cell–cell cross-talk. It is perhaps then unsurprising that several classes of plant RLKs (receptor-like kinases), as well as other membrane-localized signalling components, have been implicated both in epidermal specification and in patterning events governing the distribution of epidermal cell types. However, despite our growing knowledge of the roles of these signalling molecules, remarkably little is understood regarding their function at the cellular level. In particular the potential role of regulated proteolytic cleavage in controlling the activity of signalling molecules at the plant plasma membrane has remained largely unaddressed despite its massive importance in signalling in animal systems. Because of the relative physical accessibility of their expression domains, molecules involved in epidermal development present opportunities for investigating mechanisms of cell–cell signalling in planta. Advances in understanding the potential regulatory processing of membrane-localized signalling molecules during epidermal development will be examined using parallels with animal systems to highlight potential future directions for this field of research.

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