IκB kinase β (IKKβ) does not mediate feedback inhibition of the insulin signalling cascade

2013 ◽  
Vol 452 (1) ◽  
pp. 171-171
Author(s):  
G. I. Lancaster ◽  
B. Skiba ◽  
C. Yang ◽  
H. T. Nicholls ◽  
K. G. Langley ◽  
...  
Keyword(s):  
Feedback Inhibition ◽  
Insulin Signalling ◽  
Iκb Kinase ◽  
Signalling Cascade

IκB kinase β (IKKβ) does not mediate feedback inhibition of the insulin signalling cascade

2012 ◽  
Vol 442 (3) ◽  
pp. 723-732 ◽  
Author(s):  
Graeme I. Lancaster ◽  
Beata Skiba ◽  
Christine Yang ◽  
Hayley T. Nicholls ◽  
Katherine G. Langley ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Feedback Inhibition ◽  
Insulin Signalling ◽  
Serine Phosphorylation ◽  
Regulatory Subunit ◽  
Iκb Kinase ◽  
Pkb Phosphorylation ◽  
Signalling Cascade

In the present study, we have examined whether IKKβ [IκB (inhibitor of nuclear factor κB) kinase β] plays a role in feedback inhibition of the insulin signalling cascade. Insulin induces the phosphorylation of IKKβ, in vitro and in vivo, and this effect is dependent on intact signalling via PI3K (phosphoinositide 3-kinase), but not PKB (protein kinase B). To test the hypothesis that insulin activates IKKβ as a means of negative feedback, we employed a variety of experimental approaches. First, pharmacological inhibition of IKKβ via BMS-345541 did not potentiate insulin-induced IRS1 (insulin receptor substrate 1) tyrosine phosphorylation, PKB phosphorylation or 2-deoxyglucose uptake in differentiated 3T3-L1 adipocytes. BMS-345541 did not prevent insulin-induced IRS1 serine phosphorylation on known IKKβ target sites. Secondly, adenovirus-mediated overexpression of wild-type IKKβ in differentiated 3T3-L1 adipocytes did not suppress insulin-stimulated 2-deoxyglucose uptake, IRS1 tyrosine phosphorylation, IRS1 association with the p85 regulatory subunit of PI3K or PKB phosphorylation. Thirdly, insulin signalling was not potentiated in mouse embryonic fibroblasts lacking IKKβ. Finally, insulin treatment of 3T3-L1 adipocytes did not promote the recruitment of IKKβ to IRS1, supporting our findings that IKKβ, although activated by insulin, does not promote direct serine phosphorylation of IRS1 and does not contribute to the feedback inhibition of the insulin signalling cascade.

scholarly journals Effect of klotho as an ageing suppressor on insulin signalling cascade in brain of d-galactose mice by Yisui moxibustion

2019 ◽  
Vol 33 (1) ◽  
pp. 1343-1353
Author(s):  
Xinge Huang ◽  
Chuanli Su ◽  
Shuyan Chen ◽  
Jinlong Teng ◽  
Lihua Zhao ◽  
...  
Keyword(s):  
Insulin Signalling ◽  
Signalling Cascade

Vitis viniferaL. grape skin extract activates the insulin-signalling cascade and reduces hyperglycaemia in alloxan-induced diabetic mice

2011 ◽  
Vol 64 (2) ◽  
pp. 268-276 ◽  
Author(s):  
Roberto Soares de Moura ◽  
Giselle França da Costa ◽  
Annie Seixas Bello Moreira ◽  
Emerson Ferreira Queiroz ◽  
Daniele Dal Col Moreira ◽  
...  
Keyword(s):  
Insulin Signalling ◽  
Skin Extract ◽  
Diabetic Mice ◽  
Grape Skin ◽  
Signalling Cascade ◽  
Grape Skin Extract

scholarly journals Feedback inhibition of Ras activity coordinates cell fusion with cell-cell contact

2017 ◽  
Author(s):  
Laura Merlini ◽  
Bita Khalili ◽  
Omaya Dudin ◽  
Laetitia Michon ◽  
Vincent Vincenzetti ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Feedback Inhibition ◽  
Cell Contact ◽  
Fusion Cell ◽  
Negative Feedback Control ◽  
Local Cell ◽  
Local Enrichment ◽  
Pheromone Signalling ◽  
Signalling Cascade ◽  
Cell Cell

AbstractIn fission yeast Schizosaccharomyces pombe, pheromone signalling engages a GPCR-Ras-MAPK cascade to trigger sexual differentiation leading to gamete fusion. Cell-cell fusion necessitates local cell wall digestion, the location of which relies on an initially dynamic actin fusion focus that becomes stabilized upon local enrichment of the signalling cascade. We constructed a live-reporter of active Ras1 (Ras1-GTP), also functional in S. cerevisiae, which revealed Ras activity at polarity sites peaking on the fusion structure before fusion. Remarkably, constitutive Ras1 activation promoted fusion focus stabilization and fusion attempts irrespective of cell-cell pairing, leading to cell lysis. Ras1 activity is restricted by the GTPase activating protein (GAP) Gap1, itself recruited to sites of Ras1-GTP. While the GAP domain on its own does not suffice for this localization, its recruitment to Ras1-GTP sites is essential to block untimely fusion attempts. We conclude that negative feedback control of Ras activity restrains the MAPK signal and couples fusion with cell-cell engagement.

scholarly journals GDI-1 preferably interacts with Rab10 in insulin-stimulated GLUT4 translocation

2009 ◽  
Vol 422 (2) ◽  
pp. 229-235 ◽  
Author(s):  
Yu Chen ◽  
Yongqiang Deng ◽  
Jinzhong Zhang ◽  
Lu Yang ◽  
Xiangyang Xie ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Insulin Signalling ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Similar Distribution ◽  
Glut4 Translocation ◽  
Guanine Nucleotide Dissociation Inhibitor ◽  
Golgi Network ◽  
Signalling Cascade

Insulin stimulates GLUT4 (glucose transporter 4) translocation in adipocytes and muscles. An emerging picture is that Rab10 could bridge the gap between the insulin signalling cascade and GLUT4 translocation in adipocytes. In the present study, two potential effectors of Rab10, GDI (guanine-nucleotide-dissociation inhibitor)-1 and GDI-2, are characterized in respect to their roles in insulin-stimulated GLUT4 translocation. It is shown that both GDI-1 and GDI-2 exhibit similar distribution to GLUT4 and Rab10 at the TGN (trans-Golgi network) and periphery structures. Meanwhile, GDI-1 clearly interacts with Rab10 with higher affinity, as shown by both immunoprecipitation and in vivo FRET (fluorescence resonance energy transfer). In addition, the participation of GDIs in GLUT4 translocation is illustrated when overexpression of either GDI inhibits insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. Taken together, we propose that GDI-1 is preferentially involved in insulin-stimulated GLUT4 translocation through facilitating Rab10 recycling.

scholarly journals IκB Kinase β Phosphorylates the K63 Deubiquitinase A20 To Cause Feedback Inhibition of the NF-κB Pathway

2007 ◽  
Vol 27 (21) ◽  
pp. 7451-7461 ◽  
Author(s):  
Jessica E. Hutti ◽  
Benjamin E. Turk ◽  
John M. Asara ◽  
Averil Ma ◽  
Lewis C. Cantley ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Feedback Inhibition ◽  
Innate Immune ◽  
Negative Regulator ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Iκb Kinase ◽  
Phosphorylation Event

ABSTRACT Misregulation of NF-κB signaling leads to infectious, inflammatory, or autoimmune disorders. IκB kinase β (IKKβ) is an essential activator of NF-κB and is known to phosphorylate the NF-κB inhibitor, IκBα, allowing it to undergo ubiquitin-mediated proteasomal degradation. However, beyond IκBα, few additional IKKβ substrates have been identified. Here we utilize a peptide library and bioinformatic approach to predict likely substrates of IKKβ. This approach predicted Ser381 of the K63 deubiquitinase A20 as a likely site of IKKβ phosphorylation. While A20 is a known negative regulator of innate immune signaling pathways, the mechanisms regulating the activity of A20 are poorly understood. We show that IKKβ phosphorylates A20 in vitro and in vivo at serine 381, and we further show that this phosphorylation event increases the ability of A20 to inhibit the NF-κB signaling pathway. Phosphorylation of A20 by IKKβ thus represents part of a novel feedback loop that regulates the duration of NF-κB signaling following activation of innate immune signaling pathways.

Gentiopicroside and sweroside from Veratrilla baillonii Franch. induce phosphorylation of Akt and suppress Pck1 expression in hepatoma cells

2016 ◽  
Vol 94 (3) ◽  
pp. 270-278 ◽  
Author(s):  
Xian-Ju Huang ◽  
Jun Li ◽  
Zhi-Yi Mei ◽  
Guoxun Chen
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Insulin Signalling ◽  
Herbal Medicines ◽  
Ethanol Extract ◽  
Hepatoma Cells ◽  
Dependent Manner ◽  
Biomedical Sciences ◽  
Insulin Control ◽  
Functional Mechanisms ◽  
Signalling Cascade

The use of phytochemicals and herbal medicines has accompanied human history. Advances in modern biomedical sciences have allowed us to investigate the functional mechanisms of herbal medicines and phytochemicals. Veratrilla baillonii Franch. has long been used as a medicinal herb in southwestern China. Here, we analyzed the effects of an ethanol extract from V. baillonii (VBFE) on the expression levels of the cytosolic form of the phosphoenolpyruvate carboxykinase gene (Pck1) mRNA and components of the insulin signalling cascade in HL1C hepatoma cells. Compared with the insulin control, VBFE treatment inhibited the expression of Pck1 mRNA in a dose-dependent manner. This was associated with the phosphorylation of Akt and Erk1/2 in a time-dependent manner. Further analysis of the purified components of VBFE indicated that gentiopicroside and sweroside from VBFE, alone and in combination, suppressed Pck1 expression and induced Akt and Erk1/2 phosphorylation. In conclusion, gentiopicroside and sweroside suppress Pck1 expression and induce phosphorylation of components in the insulin signalling cascade. This is the first study to demonstrate that gentiopicroside and sweroside show insulin-mimicking effects on the regulation of Pck1 expression. Further studies are warranted to explore the potential of gentiopicroside and sweroside in the control of blood glucose in animals.

Sign in / Sign up

Export Citation Format

Share Document