ArticleProceedings of the National Academy of Sciences of the United States of America2015
Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+ NIK+ signalosome on Rab5+ endosomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 65 citations in OpenAlex.
- Internalized components of membrane attack complexes disrupt proteostasis and acquire alarmin-like properties.Nature communications · 2026Article
- Internalized Components of Membrane Attack Complexes Disrupt Proteostasis and Acquire Alarmin-Like Properties.bioRxiv : the preprint server for biology · 2026Article
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- Endothelial Cell Secretome Alterations Induced by Inflammatory Stress.bioRxiv : the preprint server for biology · 2026Article
- Pathogenesis of Chronic Rejection: Graft Endothelial Cell Trans-presentation of IL-15 Connects Alloantibody- and Cell-Mediated Steps in Allograft Vasculopathy.Results and problems in cell differentiation · 2026Review
- Intracellular C3 regulates the immune response to infection via NF-κB signaling.Cellular and molecular life sciences : CMLS · 2025Article
- Complement C4 exacerbates astrocyte-mediated neuroinflammation and promotes α-synuclein pathology in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Protein biomarkers in assessing kidney quality before transplantation‑current status and future perspectives (Review).International journal of molecular medicine · 2024Review
- NIK Is a Mediator of Inflammation and Intimal Hyperplasia in Endothelial Denudation-Induced Vascular Injury.International journal of molecular sciences · 2024Article
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- ZFYVE21 promotes endothelial nitric oxide signaling and vascular barrier function in the kidney during aging.Kidney international · 2024Article
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- The Transplant Bellwether: Endothelial Cells in Antibody-Mediated Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells.Nature communications · 2023Article
- Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells.Science signaling · 2023Article
- Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.Nature communications · 2022Article
- Neutrophils activated by membrane attack complexes increase the permeability of melanoma blood vessels.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa.Pathogens (Basel, Switzerland) · 2022Article
- Membrane attack complexes, endothelial cell activation, and direct allorecognition.Frontiers in immunology · 2022Review
- Complement membrane attack complex is an immunometabolic regulator of NLRP3 activation and IL-18 secretion in human macrophages.Frontiers in immunology · 2022Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Complement membrane attack complexes (MACs) promote inflammatory functions in endothelial cells (ECs) by stabilizing NF-κB-inducing kinase (NIK) and activating noncanonical NF-κB signaling. Here we report a novel endosome-based signaling complex induced by MACs to stabilize NIK. We found that, in contrast to cytokine-mediated activation, NIK stabilization by MACs did not involve cIAP2 or TRAF3. Informed by a genome-wide siRNA screen, instead this response required internalization of MACs in a clathrin-, AP2-, and dynamin-dependent manner into Rab5(+)endosomes, which recruited activated Akt, stabilized NIK, and led to phosphorylation of IκB kinase (IKK)-α. Active Rab5 was required for recruitment of activated Akt to MAC(+) endosomes, but not for MAC internalization or for Akt activation. Consistent with these in vitro observations, MAC internalization occurred in human coronary ECs in vivo and was similarly required for NIK stabilization and EC activation. We conclude that MACs activate noncanonical NF-κB by forming a novel Akt(+)NIK(+) signalosome on Rab5(+) endosomes.
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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.