ArticleThe Journal of biological chemistry2015
Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- Ginsenoside Rg1 attenuates experimental periodontitis via modulating the PI3K/AKT pathway and TLR2 expression.BMC oral health · 2026Article
- The Role ofCancers · 2025Review
- Lys-specific gingipain (Kgp) ofmBio · 2025Article
- Hallmarks of Periodontitis.Current medicinal chemistry · 2025Review
- The oral-gut microbiome axis in inflammatory bowel disease: from inside to insight.Frontiers in immunology · 2024Review
- Periodontitis Continuum: Antecedents, Triggers, Mediators, and Treatment Strategies.Current medicinal chemistry · 2024Review
- Metronidazole Potentiation by Panax Ginseng andAntibiotics (Basel, Switzerland) · 2023Article
- AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via BadApoptosis : an international journal on programmed cell death · 2023Article
- A comprehensive review on human disease-causing bacterial proteases and their impeding agents.Archives of microbiology · 2023Review
- Porphyromonas gingivalis Gingipains Destroy the Vascular Barrier and Reduce CD99 and CD99L2 Expression To Regulate Transendothelial Migration.Microbiology spectrum · 2023Article
- Dysregulation of Stress-Induced Translational Control byMicroorganisms · 2023Article
- Roles of bacterial extracellular vesicles in systemic diseases.Frontiers in microbiology · 2023Review
- Salivary and fecal microbiota: potential new biomarkers for early screening of colorectal polyps.Frontiers in microbiology · 2023Article
- The subversion of toll-like receptor signaling by bacterial and viral proteases during the development of infectious diseases.Molecular aspects of medicine · 2022Review
- Article
- SGK1 negatively regulates inflammatory immune responses and protects against alveolar bone loss through modulation of TRAF3 activity.The Journal of biological chemistry · 2022Article
- Microbiome-mediated incapacitation of interferon lambda production in the oral mucosa.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers.Military Medical Research · 2021Review
- Resveratrol as an Adjunctive Therapy for Excessive Oxidative Stress in Aging COVID-19 Patients.Antioxidants (Basel, Switzerland) · 2021Review
- Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Porphyromonas gingivalis is a major pathogen of periodontal diseases, including periodontitis. We have investigated the effect of P. gingivalis infection on the PI3K/Akt (protein kinase B) signaling pathway in gingival epithelial cells. Here, we found that live P. gingivalis, but not heat-killed P. gingivalis, reduced Akt phosphorylation at both Thr-308 and Ser-473, which implies a decrease in Akt activity. Actually, PI3K, which is upstream of Akt, was also inactivated by P. gingivalis. Furthermore, glycogen synthase kinase 3α/β, mammalian target of rapamycin, and Bad, which are downstream proteins in the PI3K/Akt cascade, were also dephosphorylated, a phenomenon consistent with Akt inactivation by P. gingivalis. However, these events did not require direct interaction between bacteria and host cells and were independent of P. gingivalis invasion into the cells. The use of gingipain-specific inhibitors and a gingipain-deficient P. gingivalis mutant KDP136 revealed that the gingipains and their protease activities were essential for the inactivation of PI3K and Akt. The associations between the PI3K regulatory subunit p85α and membrane proteins were disrupted by wild-type P. gingivalis. Moreover, PDK1 translocation to the plasma membrane was reduced by wild-type P. gingivalis, but not KDP136, indicating little production of phosphatidylinositol 3,4,5-triphosphate by PI3K. Therefore, it is likely that PI3K failed to transmit homeostatic extracellular stimuli to intracellular signaling pathways by gingipains. Taken together, our findings indicate that P. gingivalis attenuates the PI3K/Akt signaling pathway via the proteolytic effects of gingipains, resulting in the dysregulation of PI3K/Akt-dependent cellular functions and the destruction of epithelial barriers.
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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.