ArticleThe Journal of biological chemistry2011
Feedback regulation of endothelial cell surface plasmin generation by PKC-dependent phosphorylation of annexin A2.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- ANXA2 in cancer: aberrant regulation of tumour cell apoptosis and its immune interactions.Cell death discovery · 2025Review
- Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression.Frontiers in oncology · 2023Article
- Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation.Pathogens (Basel, Switzerland) · 2021Article
- Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy.Cancers · 2021Review
- Annexin Animal Models-From Fundamental Principles to Translational Research.International journal of molecular sciences · 2021Review
- Article
- Exchange protein directly activated by cAMP plays a critical role in regulation of vascular fibrinolysis.Life sciences · 2019Article
- Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2019Article
- Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)Cell death & disease · 2018Article
- Annexins in Translational Research: Hidden Treasures to Be Found.International journal of molecular sciences · 2018Review
- Regulation of von-Willebrand Factor Secretion from Endothelial Cells by the Annexin A2-S100A10 Complex.International journal of molecular sciences · 2018Review
- Involvement of Pro-Inflammatory Macrophages in Liver Pathology of Pirital Virus-Infected Syrian Hamsters.Viruses · 2018Article
- EPAC1 regulates endothelial annexin A2 cell surface translocation and plasminogen activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Post-translational modifications of Annexin A2 are linked to its association with perinuclear nonpolysomal mRNP complexes.FEBS open bio · 2017Article
- CC chemokine receptor 10 cell surface presentation in melanocytes is regulated by the novel interaction partner S100A10.Scientific reports · 2016Article
- CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling.Oncotarget · 2016Article
- Expression and significance of annexin A2 in patients with gastric adenocarcinoma and the association with E-cadherin.Experimental and therapeutic medicine · 2015Article
- The Biology of Annexin A2: From Vascular Fibrinolysis to Innate Immunity.Transactions of the American Clinical and Climatological Association · 2015Review
- The inflammatory actions of coagulant and fibrinolytic proteases in disease.Mediators of inflammation · 2015Review
- Annexin II-dependent actin remodelling evoked by hydrogen peroxide requires the metalloproteinase/sphingolipid pathway.Redox biology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In response to blood vessel injury, hemostasis is initiated by platelet activation, advanced by thrombin generation, and tempered by fibrinolysis. The primary fibrinolytic protease, plasmin, can be activated either on a fibrin-containing thrombus or on cells. Annexin A2 (A2) heterotetramer (A2·p11)(2) is a key profibrinolytic complex that assembles plasminogen and tissue plasminogen activator and promotes plasmin generation. We now report that, in endothelial cells, plasmin specifically induces activation of conventional PKC, which phosphorylates serine 11 and serine 25 of A2, triggering dissociation of the (A2·p11)(2) tetramer. The resulting free p11 undergoes ubiquitin-mediated proteasomal degradation, thus preventing further translocation of A2 to the cell surface. In vivo, pretreatment of A2(+/+) but not A2(-/-) mice with a conventional PKC inhibitor significantly reduced thrombosis in a carotid artery injury model. These results indicate that augmentation of fibrinolytic vascular surveillance by blockade of serine phosphorylation is A2-dependent. We also demonstrate that plasmin-induced phosphorylation of A2 requires both cleavage of A2 and activation of Toll-like receptor 4 on the cell surface. We propose that plasmin can limit its own generation by triggering a finely tuned "feedback" mechanism whereby A2 becomes serine-phosphorylated, dissociates from p11, and fails to translocate to the cell surface.
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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.