{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:41:35Z","timestamp":1773416495554,"version":"3.50.1"},"reference-count":37,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diarrhea-associated hemolytic uremic syndrome (D+HUS) is caused by the ingestion of Escherichia coli that produce Shiga toxin (Stx), which is composed of a cytotoxic A subunit and pentameric B subunits that bind globotriaosylceramide on susceptible cells. Stx occurs in 2 types, Stx1 and Stx2. B subunits of either type stimulate von Willebrand factor (VWF) secretion from human umbilical vein endothelial cells (HUVECs), and Stx2B can cause thrombotic microangiopathy in Adamts13\u2212\/\u2212 mice. We have now determined that Stx1B and Stx2B activate different signaling pathways in HUVECs. VWF secretion induced by Stx1B is associated with a transient rise in intracellular Ca2+ level that is blocked by chelation with 1,2-bis(2-aminophenoxy)ethane-N,N,N\u2032,N\u2032-tetraacetic acid-acetoxymethyl ester, removal of extracellular Ca2+, the phospholipase C inhibitor U73122, the protein kinase inhibitor staurosporine, or small interfering RNA knockdown of protein kinase C\u03b1. In contrast, Stx2B-induced VWF secretion is associated with activation of protein kinase A (PKA) and is blocked by the PKA inhibitor H89 or small interfering RNA knockdown of PKA. Stx2B does not increase cAMP levels and may activate PKA by a cAMP-independent mechanism. The activation of distinct signaling pathways may be relevant to understanding why E coli that express Stx2 are more likely to cause D+HUS than are E coli expressing only Stx1.<\/jats:p>","DOI":"10.1182\/blood-2011-06-363648","type":"journal-article","created":{"date-parts":[[2011,8,5]],"date-time":"2011-08-05T00:18:10Z","timestamp":1312503490000},"page":"3392-3398","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":35,"title":["Shiga toxin (Stx)1B and Stx2B induce von Willebrand factor secretion from human umbilical vein endothelial cells through different signaling pathways"],"prefix":"10.1182","volume":"118","author":[{"given":"Fang","family":"Liu","sequence":"first","affiliation":[{"name":"Departments of Medicine, and"},{"name":"Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"Departments of Medicine, and"},{"name":"Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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