PTEN Directly Activates the Actin Depolymerization Factor Cofilin-1 During PGE(2)-Mediated Inhibition of Phagocytosis of Fungi

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dc.contributor.authorSerezani, C. Henrique
dc.contributor.authorKane, Steve
dc.contributor.authorMedeiros, Alexandra Ivo de [UNESP]
dc.contributor.authorCornett, Ashley M.
dc.contributor.authorKim, Sang-Hoon
dc.contributor.authorMarques, Mariana Morato
dc.contributor.authorLee, Sang-Pyo
dc.contributor.authorLewis, Casey
dc.contributor.authorBourdonnay, Emilie
dc.contributor.authorBallinger, Megan N.
dc.contributor.authorWhite, Eric S.
dc.contributor.authorPeters-Golden, Marc
dc.contributor.institutionUniversity of Michigan
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionEulji Univ
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionGachon Univ Gil Hosp
dc.date.accessioned2014-05-20T13:24:12Z
dc.date.available2014-05-20T13:24:12Z
dc.date.issued2012-02-07
dc.description.abstractMacrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E-2 (PGE(2)) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE(2)-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE(2) suppressed phagocytosis and F-actin formation through the PGE(2) receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE(2). PGE(2)-dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE(2) accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses.en
dc.description.affiliationUniv Michigan Hlth Syst, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA
dc.description.affiliationSão Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Biol Sci, BR-14801902 Araraquara, Brazil
dc.description.affiliationEulji Univ, Sch Med, Dept Internal Med, Div Allergy & Resp Med, Seoul 139711, South Korea
dc.description.affiliationUniv São Paulo, Inst Biomed Sci 4, Dept Immunol, BR-05508000 São Paulo, Brazil
dc.description.affiliationGachon Univ Gil Hosp, Div Allergy, Inchon 405760, South Korea
dc.description.affiliationUnespSão Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Biol Sci, BR-14801902 Araraquara, Brazil
dc.description.sponsorshipNIH
dc.description.sponsorshipAmerican Lung Association
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdNIH: HL058897
dc.description.sponsorshipIdNIH: K99HL103777
dc.description.sponsorshipIdNIH: HL085083
dc.description.sponsorshipIdCNPq: 201061/2007-4
dc.format.extent10
dc.identifierhttp://dx.doi.org/10.1126/scisignal.2002448
dc.identifier.citationScience Signaling. Washington: Amer Assoc Advancement Science, v. 5, n. 210, p. 10, 2012.
dc.identifier.doi10.1126/scisignal.2002448
dc.identifier.issn1937-9145
dc.identifier.urihttp://hdl.handle.net/11449/7443
dc.identifier.wosWOS:000300610300002
dc.language.isoeng
dc.publisherAmer Assoc Advancement Science
dc.relation.ispartofScience Signaling
dc.relation.ispartofsjr3,812
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.titlePTEN Directly Activates the Actin Depolymerization Factor Cofilin-1 During PGE(2)-Mediated Inhibition of Phagocytosis of Fungien
dc.typeArtigo
dcterms.licensehttp://www.sciencemag.org/site/feature/contribinfo/prep/license.xhtml
dcterms.rightsHolderAmer Assoc Advancement Science
unesp.author.lattes8756770929017974[3]
unesp.author.orcid0000-0001-6048-3647[3]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt
unesp.departmentCiências Biológicas - FCFpt

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Araraquara - FCF - Faculdade de Ciências Farmacêuticas