{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nigro P"],"funding":["NHLBI NIH HHS"],"pagination":["1971-9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3173991"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["116(11)"],"pubmed_abstract":["PKCζ has emerged as a pathologic mediator of endothelial cell dysfunction, based on its essential role in tumor necrosis factor α (TNFα)-mediated inflammation. In contrast, extracellular signal-regulated kinase 5 (ERK5) function is required for endothelial cell homeostasis as shown by activation of Krüppel-like factor 2 (KLF2), increased endothelial nitric-oxide synthase (eNOS) expression, and inhibition of apoptosis. We hypothesized that protein kinase C ζ (PKCζ) activation by TNFα would inhibit the ERK5/KLF2/eNOS pathway. TNFα inhibited the steady laminar flow-induced eNOS expression, and this effect was reversed by the dominant-negative form of PKCζ (Ad.DN-PKCζ). In addition, ERK5 function was inhibited by either TNFα or the transfection of the catalytic domain of PKCζ. This inhibition "],"journal":["Blood"],"pubmed_title":["PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5."],"pmcid":["PMC3173991"],"funding_grant_id":["R01 HL088637","P01 HL077789-05","HL-064839","P01 HL077789","HL-077789","R01 HL102746","HL-088637","R01 HL064839","R01 HL064839-10"],"pubmed_authors":["Fujiwara K","Li JD","McClain C","Lim JH","Heo KS","Berk BC","Nigro P","Woo CH","Lee H","Satoh K","Abe J","O'Dell MR"],"additional_accession":[]},"is_claimable":false,"name":"PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5.","description":"PKCζ has emerged as a pathologic mediator of endothelial cell dysfunction, based on its essential role in tumor necrosis factor α (TNFα)-mediated inflammation. In contrast, extracellular signal-regulated kinase 5 (ERK5) function is required for endothelial cell homeostasis as shown by activation of Krüppel-like factor 2 (KLF2), increased endothelial nitric-oxide synthase (eNOS) expression, and inhibition of apoptosis. We hypothesized that protein kinase C ζ (PKCζ) activation by TNFα would inhibit the ERK5/KLF2/eNOS pathway. TNFα inhibited the steady laminar flow-induced eNOS expression, and this effect was reversed by the dominant-negative form of PKCζ (Ad.DN-PKCζ). In addition, ERK5 function was inhibited by either TNFα or the transfection of the catalytic domain of PKCζ. This inhibition ","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Sep","modification":"2025-05-29T22:12:02.32Z","creation":"2025-05-29T22:12:02.32Z"},"accession":"S-EPMC3173991","cross_references":{"pubmed":["20538799"],"doi":["10.1182/blood-2010-02-269134"]}}