ArticleInfection and immunity2007
Leishmania donovani-induced ceramide as the key mediator of Akt dephosphorylation in murine macrophages: role of protein kinase Czeta and phosphatase.
Article in Infection and immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Manipulation of macrophage signaling byVirulence · 2025Review
- Cancer stem cells and ceramide signaling: the cutting edges of immunotherapy.Molecular biology reports · 2020Review
- PKCζ mediated anti-proliferative effect of C2 ceramide on neutralization of the tumor microenvironment and melanoma regression.Cancer immunology, immunotherapy : CII · 2020Article
- TNFα mediated ceramide generation triggers cisplatin induced apoptosis in B16F10 melanoma in a PKCδ independent manner.Oncotarget · 2018Article
- Function of Macrophage and Parasite Phosphatases in Leishmaniasis.Frontiers in immunology · 2017Review
- Leishmania donovani Utilize Sialic Acids for Binding and Phagocytosis in the Macrophages through Selective Utilization of Siglecs and Impair the Innate Immune Arm.PLoS neglected tropical diseases · 2016Article
- Spatio-Temporal Regulation of PKC Isoforms Imparts Signaling Specificity.Frontiers in immunology · 2016Review
- Article
- Hitting the golden TORget: curcumin's effects on mTOR signaling.Anti-cancer agents in medicinal chemistry · 2013Review
- Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis.Seminars in immunopathology · 2012Review
- Sphingolipid degradation by Leishmania major is required for its resistance to acidic pH in the mammalian host.Infection and immunity · 2011Article
- Evasion of Host Defence by Leishmania donovani: Subversion of Signaling Pathways.Molecular biology international · 2011Article
- Article
- Cancer treatment strategies targeting sphingolipid metabolism.Advances in experimental medicine and biology · 2010Review
- Leishmania interferes with host cell signaling to devise a survival strategy.Journal of biomedicine & biotechnology · 2010Review
- Degradation of host sphingomyelin is essential for Leishmania virulence.PLoS pathogens · 2009Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania donovani is an intracellular protozoan parasite that impairs the host macrophage immune response to render it suitable for its survival and establishment. L. donovani-induced immunosuppression and alteration of host cell signaling is mediated by ceramide, a pleiotropic second messenger playing an important role in regulation of several kinases, including mitogen-activated protein kinase and phosphatases. We observed that the endogenous ceramide generated during leishmanial infection led to the dephosphorylation of protein kinase B (PKB) (Akt) in infected cells. The study of ceramide-mediated Akt phosphorylation revealed that Akt was dephosphorylated at both Thr308 and Ser473 sites in infected cells. Further investigation demonstrated that ceramide was also responsible for the induction of PKCzeta, an atypical Ca-independent stress kinase, as well as the ceramide-activated protein phosphatases (e.g., protein phosphatase 2A [PP2A]). We found that Akt dephosphorylation was mediated by ceramide-induced PKCzeta-Akt association and PP2A activation. In addition, treatment of L. donovani-infected macrophages with PKCzeta-specific inhibitor peptide could restore the translocation of phosphorylated Akt to the cell membrane. This study also revealed that ceramide is involved in the inhibition of proinflammatory cytokine tumor necrosis factor alpha release by infected macrophages. These observations strongly suggest the importance of ceramide in the alteration of normal cellular functions, impairment of the kinase/phosphatase balance, and thereby establishment of leishmaniasis in the hostile macrophage environment.
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