ArticleThe Journal of biological chemistry2015
Cleavage of Signal Regulatory Protein α (SIRPα) Enhances Inflammatory Signaling.
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 40 papers.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- SIRPα Cleavage Is Associated with Inflammatory Response, Corticosteroid Nonresponse, and Worse Prognosis in Clinical and Preclinical Models of Alcohol-Associated Hepatitis.The American journal of pathology · 2026Article
- SIRPα extracellular domain shed from neutrophils by ADAM10 aggravates sepsis via initiating nitric oxide release from erythrocyte.Journal of advanced research · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Targeting the CD47-SIRPα Axis in Atherosclerosis: From Pathogenesis to Therapeutic Implications.Journal of inflammation research · 2026Review
- Review
- Molecular Mechanisms Underlying Differences in Athletic Ability in Racehorses Based on Whole Transcriptome Sequencing.Biology · 2025Article
- Inhibitory pattern recognition receptors: lessons from LAIR1.Nature reviews. Immunology · 2025Review
- Functional Differences Between SIRPα Splice Isoforms.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer's disease through disrupted regulated intramembrane proteolysis.Molecular neurodegeneration · 2025Article
- Macrophages in prostate cancer: dual roles in tumor progression and immune evasion.Journal of translational medicine · 2025Review
- Novel immunotherapy for gastric cancer: targeting the CD47-SIRPα axis.Cancer metastasis reviews · 2025Review
- Circulating Monocytes Contribute to Erythrocyte Clearance in Polycythemia Vera.International journal of molecular sciences · 2025Article
- Biochemical and biophysical mechanisms macrophages use to tune phagocytic appetite.Journal of cell science · 2025Review
- Monocyte-red blood cell crosstalk supports clearance and heme metabolism in sickle cell anemia.Frontiers in immunology · 2025Article
- Oxidative stress-driven enhanced iron production and scavenging through Ferroportin reorientation worsens anemia in antimony-resistant Leishmania donovani infection.PLoS pathogens · 2025Article
- The expression of signal regulatory protein alpha (SIRPα) in periodontal cells and tissue.Acta odontologica Scandinavica · 2024Article
- Tolerating CD47.Clinical and translational medicine · 2024Review
- The TSP1-CD47-SIRPα interactome: an immune triangle for the checkpoint era.Cancer immunology, immunotherapy : CII · 2023Review
- ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Signal regulatory protein α (SIRPα) is a membrane glycoprotein immunoreceptor abundant in cells of monocyte lineage. SIRPα ligation by a broadly expressed transmembrane protein, CD47, results in phosphorylation of the cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, resulting in the inhibition of NF-κB signaling in macrophages. Here we observed that proteolysis of SIRPα during inflammation is regulated by a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), resulting in the generation of a membrane-associated cleavage fragment in both THP-1 monocytes and human lung epithelia. We mapped a charge-dependent putative cleavage site near the membrane-proximal domain necessary for ADAM10-mediated cleavage. In addition, a secondary proteolytic cleavage within the membrane-associated SIRPα fragment by γ-secretase was identified. Ectopic expression of a SIRPα mutant plasmid encoding a proteolytically resistant form in HeLa cells inhibited activation of the NF-κB pathway and suppressed STAT1 phosphorylation in response to TNFα to a greater extent than expression of wild-type SIRPα. Conversely, overexpression of plasmids encoding the proteolytically cleaved SIRPα fragments in cells resulted in enhanced STAT-1 and NF-κB pathway activation. Thus, the data suggest that combinatorial actions of ADAM10 and γ-secretase on SIRPα cleavage promote inflammatory signaling.
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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.