ArticleInsect biochemistry and molecular biology2020
Inhibition of immune pathway-initiating hemolymph protease-14 by Manduca sexta serpin-12, a conserved mechanism for the regulation of melanization and Toll activation in insects.
Article in Insect biochemistry and molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Partial reconstitution of the prophenoloxidase activation system inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Innate Immunity in Insects: The Lights and Shadows of Phenoloxidase System Activation.International journal of molecular sciences · 2025Review
- Invertebrate Immunity, Natural Transplantation Immunity, Somatic and Germ Cell Parasitism, and Transposon Defense.International journal of molecular sciences · 2024Review
- Parasitoid Serpins Evolve Novel Functions to Manipulate Host Homeostasis.Molecular biology and evolution · 2023Article
- Serpin-1a and serpin-6 regulate the Toll pathway immune homeostasis by synergistically inhibiting the Spätzle-processing enzyme CLIP2 in silkworm, Bombyx mori.PLoS pathogens · 2023Article
- Two venom serpins from the parasitoid wasp Microplitis mediator inhibit the host prophenoloxidase activation and antimicrobial peptide synthesis.Insect biochemistry and molecular biology · 2023Article
- Proteomic analysis of pharate pupal molting fluid from the tobacco hornworm, Manduca sexta.Insect biochemistry and molecular biology · 2022Article
- A fat body transcriptome analysis of the immune responses of Rhodnius prolixus to artificial infections with bacteria.Parasites & vectors · 2022Article
- Serpin-4 Facilitates Baculovirus Infection by Inhibiting Melanization in Asian Corn Borer,Frontiers in immunology · 2022Article
- Haemocyte-mediated immunity in insects: Cells, processes and associated components in the fight against pathogens and parasites.Immunology · 2021Review
- Sexual conflict drives micro- and macroevolution of sexual dimorphism in immunity.BMC biology · 2021Article
- The CLIP-domain serine protease CLIPC9 regulates melanization downstream of SPCLIP1, CLIPA8, and CLIPA28 in the malaria vector Anopheles gambiae.PLoS pathogens · 2020Article
- Hemolymph protease-5 links the melanization and Toll immune pathways in the tobacco hornworm,Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- CLIPB10 is a Terminal Protease in the Regulatory Network That Controls Melanization in the African Malaria MosquitoFrontiers in cellular and infection microbiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
A network of serine proteases (SPs) and their non-catalytic homologs (SPHs) activates prophenoloxidase (proPO), Toll pathway, and other insect immune responses. However, integration and conservation of the network and its control mechanisms have not yet been fully understood. Here we present evidence that these responses are initiated through a conserved serine protease and negatively regulated by serpins in two species, Manduca sexta and Anopheles gambiae. We have shown that M. sexta serpin-12 reduces the proteolytic activation of HP6, HP8, proPO activating proteases (PAPs), SPHs, and POs in larval hemolymph, and we hypothesized that these effects are due to the inhibition of the immune pathway-initiating protease HP14. To test whether these changes are due to HP14 inhibition, we isolated a covalent complex of HP14 with serpin-12 from plasma using polyclonal antibodies against the HP14 protease domain or against serpin-12, and confirmed formation of the complex by 2D-electrophoresis, immunoblotting, and mass spectrometry. Upon recognition of bacterial peptidoglycans or fungal β-1,3-glucan, the zymogen proHP14 became active HP14, which formed an SDS-stable complex with serpin-12 in vitro. Activation of proHP21 by HP14 was suppressed by serpin-12, consistent with the decrease in steps downstream of HP21, proteolytic activation of proPAP3, proSPH1/2 and proPO in hemolymph. Guided by the results of phylogenetic analysis, we cloned and expressed A. gambiae proSP217 (an ortholog of HP14) and core domains of A. gambiae serpin-11 and -17. The recombinant SP217 zymogen became active during expression, with cleavage between Tyr
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.