Role of p38 MAP kinase pathway in a toxin-induced model of hemolytic uremic syndrome

2004 ◽  
Vol 19 (8) ◽  
Author(s):  
XueJun Fu ◽  
Kazumoto Iijima ◽  
Kandai Nozu ◽  
Kiyoshi Hamahira ◽  
Ryojiro Tanaka ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Uremic Syndrome ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans

PLoS Genetics ◽  
2016 ◽  
Vol 12 (4) ◽  
pp. e1006010 ◽  
Author(s):  
Serena A. D’Souza ◽  
Luckshi Rajendran ◽  
Rachel Bagg ◽  
Louis Barbier ◽  
Derek M. van Pel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Caenorhabditis Elegans ◽  
Map Kinase ◽  
Motor Neurons ◽  
Leading Edge ◽  
P38 Map Kinase ◽  
Endosomal Trafficking ◽  
Guidance Cue ◽  
Map Kinase Pathway ◽  
Kinase Pathway

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle’s plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue.

scholarly journals The PI 3-kinase-Rac-p38 MAP kinase pathway is involved in the formation of signet-ring cell carcinoma

Oncogene ◽  
2003 ◽  
Vol 22 (36) ◽  
pp. 5537-5544 ◽  
Author(s):  
Qingyun Xu ◽  
Yutaka Karouji ◽  
Michimoto Kobayashi ◽  
Sayoko Ihara ◽  
Hiroaki Konishi ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Carcinoma ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
P38 Map Kinase ◽  
Signet Ring ◽  
Ring Cell ◽  
Map Kinase Pathway ◽  
Kinase Pathway

Activation of the p38 Map kinase pathway is essential for the antileukemic effects of dasatinib

2009 ◽  
pp. 1-13 ◽  
Author(s):  
Disha Dumka ◽  
Poonam Puri ◽  
Nathalie Carayol ◽  
Crystal Lumby ◽  
Harikrishnan Balachandran ◽  
...  
Keyword(s):  
Map Kinase ◽  
P38 Map Kinase ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals Alamandine reduces leptin expression through the c-Src/p38 MAP kinase pathway in adipose tissue

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0178769 ◽  
Author(s):  
Tsuyoshi Uchiyama ◽  
Fumikazu Okajima ◽  
Chihiro Mogi ◽  
Ayaka Tobo ◽  
Shoichi Tomono ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Map Kinase Pathway ◽  
Leptin Expression ◽  
Kinase Pathway

scholarly journals Extracellular Zinc Triggers ERK-dependent Activation of Na+/H+Exchange in Colonocytes Mediated by the Zinc-sensing Receptor

2004 ◽  
Vol 279 (50) ◽  
pp. 51804-51816 ◽  
Author(s):  
Hagit Azriel-Tamir ◽  
Haleli Sharir ◽  
Betty Schwartz ◽  
Michal Hershfinkel
Keyword(s):  
Cell Proliferation ◽  
Map Kinase ◽  
Ph Homeostasis ◽  
Ht29 Cells ◽  
Intracellular Release ◽  
Map Kinase Pathway ◽  
Zinc Sensing ◽  
Multiple Signaling ◽  
Kinase Pathway

Extracellular zinc promotes cell proliferation and its deficiency leads to impairment of this process, which is particularly important in epithelial cells. We have recently characterized a zinc-sensing receptor (ZnR) linking extracellular zinc to intracellular release of calcium. In the present study, we addressed the role of extracellular zinc, acting via the ZnR, in regulating the MAP kinase pathway and Na+/H+exchange in colonocytes. We demonstrate that Ca2+release, mediated by the ZnR, induces phosphorylation of ERK1/2, which is highly metal-specific, mediated by physiological concentrations of extracellular Zn2+but not by Cd2+, Fe2+, Ni2+, or Mn2+. Desensitization of the ZnR by Zn2+, is followed by ∼90% inhibition of the Zn2+-dependent ERK1/2 phosphorylation, indicating that the ZnR is a principal link between extracellular Zn2+and ERK1/2 activation. Application of both the IP3pathway and PI 3-kinase antagonists largely inhibited Zn2+-dependent ERK1/2 phosphorylation. The physiological significance of the Zn2+-dependent activation of ERK1/2 was addressed by monitoring Na+/H+exchanger activity in HT29 cells and in native colon epithelium. Preincubation of the cells with zinc was followed by robust activation of Na+/H+exchange, which was eliminated by cariporide (0.5 μm); indicating that zinc enhances the activity of NHE1. Activation of NHE1 by zinc was totally blocked by the ERK1/2 inhibitor, U0126. Prolonged acidification, in contrast, stimulates NHE1 by a distinct pathway that is not affected by extracellular Zn2+or inhibitors of the MAP kinase pathway. Desensitization of ZnR activity eliminates the Zn2+-dependent, but not the prolonged acidification-dependent activation of NHE1, indicating that Zn2+-dependent activation of H+extrusion is specifically mediated by the ZnR. Our results support a role for extracellular zinc, acting through the ZnR, in regulating multiple signaling pathways that affect pH homeostasis in colonocytes. Furthermore activation of both, ERK and NHE1, by extracellular zinc may provide the mechanism linking zinc to enhanced cell proliferation.

Inhibition of the p38 MAP kinase pathway destabilizes smooth muscle length during physiological loading

2002 ◽  
Vol 282 (5) ◽  
pp. L1117-L1121 ◽  
Author(s):  
Oren J. Lakser ◽  
Robert P. Lindeman ◽  
Jeffrey J. Fredberg
Keyword(s):  
Smooth Muscle ◽  
Map Kinase ◽  
Muscle Length ◽  
P38 Map Kinase ◽  
Force Fluctuations ◽  
Physiological Loading ◽  
Mitogen Activated Protein ◽  
Equilibrium Length ◽  
Map Kinase Pathway ◽  
Kinase Pathway

We tested the hypothesis that mechanical plasticity of airway smooth muscle may be mediated in part by the p38 mitogen-activated protein (MAP) kinase pathway. Bovine tracheal smooth muscle (TSM) strips were mounted in a muscle bath and set to their optimal length, where the active force was maximal (Fo). Each strip was then contracted isotonically (at 0.32 Fo) with ACh (maintained at 10−4 M) and allowed to shorten for 180 min, by which time shortening was completed and the static equilibrium length was established. To simulate the action of breathing, we then superimposed on this steady distending force a sinusoidal force fluctuation with zero mean, at a frequency of 0.2 Hz, and measured incremental changes in muscle length. We found that TSM strips incubated in 10 μM SB-203580-HCl, an inhibitor of the p38 MAP kinase pathway, demonstrated a greater degree of fluctuation-driven lengthening than did control strips, and upon removal of the force fluctuations they remained at a greater length. We also found that the force fluctuations themselves activated the p38 MAP kinase pathway. These findings are consistent with the hypothesis that inhibition of the p38 MAP kinase pathway destabilizes muscle length during physiological loading.

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