ArticleThe Journal of biological chemistry2009
The Leishmania surface protease GP63 cleaves multiple intracellular proteins and actively participates in p38 mitogen-activated protein kinase inactivation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 138 citations in OpenAlex.
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- Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms.Immune network · 2024Review
- Apoptosis and its pathways as targets for intracellular pathogens to persist in cells.Parasitology research · 2023Review
- Extracellular Vesicles and Their Impact on the Biology of Protozoan Parasites.Tropical medicine and infectious disease · 2023Review
- In-vitro biological evaluation of 3,3',5,5'-tetramethoxy-biphenyl-4,4'-diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti-leishmania potential.Scientific reports · 2023Article
- Unrevealing the Mystery of Latent Leishmaniasis: What Cells Can HostPathogens (Basel, Switzerland) · 2023Review
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- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Revisiting Leishmania GP63 host cell targets reveals a limited spectrum of substrates.PLoS pathogens · 2022Article
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- Three types ofFrontiers in cellular and infection microbiology · 2022Article
- The state of the art of extracellular vesicle research in protozoan infection.Frontiers in genetics · 2022Review
- Variation in Leishmania chemokine suppression driven by diversification of the GP63 virulence factor.PLoS neglected tropical diseases · 2021Article
- Proteins of the Ciliated Protozoan ParasitePathogens (Basel, Switzerland) · 2021Article
- Potential biomarkers of immune protection in human leishmaniasis.Medical microbiology and immunology · 2021Review
- Mining oomycete proteomes for metalloproteases leads to identification of candidate virulence factors in Phytophthora infestans.Molecular plant pathology · 2021Article
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Leishmania parasite is a widespread disease threat in tropical areas, causing symptoms ranging from skin lesions to death. Leishmania parasites typically invade macrophages but are also capable of infecting fibroblasts, which may serve as a reservoir for recurrent infection. Invasion by intracellular pathogens often involves exploitation of the host cell cytoskeletal and signaling machinery. Here we have observed a dramatic rearrangement of the actin cytoskeleton and marked modifications in the profile of protein tyrosine phosphorylation in fibroblasts infected with Leishmania major. Correspondingly, exposure to L. major resulted in degradation of the phosphorylated adaptor protein p130Cas and the protein-tyrosine phosphatase-PEST. Cellular and in vitro assays using pharmacological protease inhibitors, recombinant enzyme, and genetically modified strains of L. major identified the parasite protease GP63 as the principal catalyst of proteolysis during infection. A number of additional signaling proteins were screened for degradation during L. major infection as follows: a small subset was cleaved, including cortactin, T-cell protein-tyrosine phosphatase, and caspase-3, but the majority remained unaffected. Protein degradation occurred in cells incubated with Leishmania extracts in the absence of intact parasites, suggesting a mechanism permitting transfer of functional GP63 into the intracellular space. Finally, we evaluated the impact of Leishmania on MAPK signaling; unlike p44/42 and JNK, p38 was inactivated upon infection in a GP63- and protein degradation-dependent manner, which likely involves cleavage of the upstream adaptor TAB1. Our results establish that GP63 plays a central role in a number of hostcell molecular events that likely contribute to the infectivity of Leishmania.
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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.