title: Protein kinase CK2/PTEN pathway plays a key role in platelet-activating factor-mediated murine anaphylactic shock.
abstract: Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate. In this study, we examined the possible involvement of PTEN in PAF-mediated anaphylactic shock. Induction of anaphylaxis or PAF injection resulted in a rapid decrease in PTEN activity, followed by increases in PI3K activity and phosphorylation of Akt and eNOS. Systemic administration of adenoviruses carrying PTEN cDNA (adenoviral PTEN), but not the control AdLacZ, not only attenuated anaphylactic symptoms, but also reversed anaphylaxis- or PAF-induced changes in PTEN and PI3K activities, as well as phosphorylation of Akt and eNOS. We found that the decreased PTEN activity was associated with PTEN phosphorylation, the latter effect being prevented by the protein kinase CK2 inhibitor, DMAT. DMAT also inhibited anaphylactic symptoms as well as the anaphylaxis- or PAF-mediated PTEN/PI3K/Akt/eNOS signaling cascade. CK2 activity was increased by PAF. The present data provide, as the key mechanism underlying anaphylactic shock, PAF triggers the upstream pathway CK2/PTEN, which ultimately leads to the activation of PI3K/Akt/eNOS. Therefore, CK2/PTEN may be a potent target in the control of anaphylaxis and other many PAF-mediated pathologic conditions.
authors.affiliation: Department of Immunology, Chonbuk National University Medical School, Jeonju 561-180, Republic of Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Kang
authors.forename: Ha-Yong
authors.initials: HY
authors.lastname: Yoon
authors.forename: Han-A
authors.initials: HA
authors.lastname: Kim
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Han
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Pyoung-Han
authors.initials: PH
authors.lastname: Hwang
authors.forename: Byoung-Yul
authors.initials: BY
authors.lastname: Soh
authors.forename: Sook-Jeong
authors.initials: SJ
authors.lastname: Shin
authors.forename: Suhn-Young
authors.initials: SY
authors.lastname: Im
authors.forename: Hern-Ku
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D015153:Blotting, Western; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010972:Platelet Activating Factor; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C492322:2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole; D001562:Benzimidazoles; D010972:Platelet Activating Factor; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D047390:Casein Kinase II; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse