ArticleMolecular biology of the cell2008
The Mitogen-activated protein kinase p38 links Shiga Toxin-dependent signaling and trafficking.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Small molecules targeting endocytic uptake and recycling pathways.Frontiers in cell and developmental biology · 2023Review
- Review
- Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling.The Journal of cell biology · 2021Article
- Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy.Toxins · 2020Review
- Functional dissection of the retrograde Shiga toxin trafficking inhibitor Retro-2.Nature chemical biology · 2020Article
- The role of PS 18:0/18:1 in membrane function.Nature communications · 2019Review
- Protection against Shiga Toxins.Toxins · 2017Review
- Cross-linking of glycosphingolipids at the plasma membrane: consequences for intracellular signaling and traffic.Cellular and molecular life sciences : CMLS · 2016Article
- Activation of the Classical Mitogen-Activated Protein Kinases Is Part of the Shiga Toxin-Induced Ribotoxic Stress Response and May Contribute to Shiga Toxin-Induced Inflammation.Infection and immunity · 2016Article
- Article
- Retrograde trafficking of AB₅ toxins: mechanisms to therapeutics.Journal of molecular medicine (Berlin, Germany) · 2013Review
- Retrograde transport of protein toxins through the Golgi apparatus.Histochemistry and cell biology · 2013Review
- MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation.Infection and immunity · 2013Article
- The B subunits of Shiga-like toxins induce regulated VWF secretion in a phospholipase D1-dependent manner.Blood · 2012Article
- Mobile effector proteins on phage genomes.Bacteriophage · 2012Article
- Ricin and Shiga toxins: effects on host cell signal transduction.Current topics in microbiology and immunology · 2012Review
- Article
- Immune regulatory activities of early secreted antigenic target of 6-kD protein of Mycobacterium tuberculosis and implications for tuberculosis vaccine design.Tuberculosis (Edinburgh, Scotland) · 2011Review
- Article
- Association of botulinum neurotoxin serotype A light chain with plasma membrane-bound SNAP-25.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shiga toxin (Stx) binds to the cell, and it is transported via endosomes and the Golgi apparatus to the endoplasmic reticulum and cytosol, where it exerts its toxic effect. We have recently shown that Stx activates the tyrosine kinase Syk, which in turn induces clathrin phosphorylation and up-regulates Stx uptake. Here, we show that toxin-induced signaling can also regulate another step in intracellular Stx transport. We demonstrate that transport of Stx to the Golgi apparatus is dependent on the mitogen-activated protein kinase p38. Treatment of cells with chemical inhibitors or small interfering RNA targeting p38 inhibited Stx transport to the Golgi and reduced Stx toxicity. This p38 dependence is specific to Stx, because transport of the related toxin ricin was not affected by p38 inhibition. Stx rapidly activated p38, and recruited it to early endosomes in a Ca(2+)-dependent manner. Furthermore, agonist-induced oscillations in cytosolic Ca(2+) levels were inhibited upon Stx stimulation, possibly reflecting Stx-dependent local alterations in cytosolic Ca(2+) levels. Intracellular transport of Stx is Ca(2+) dependent, and we provide evidence that Stx activates a signaling cascade involving cross talk between Ca(2+) and p38, to regulate its trafficking to the Golgi apparatus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.