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[{"key": "dc.contributor.author", "value": "Kuronen, Ilari", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2014-04-28T13:58:51Z", "language": "", "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2014-04-28T13:58:51Z", "language": "", "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2013", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1360054", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/43295", "language": "", "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Epidermaalinen kasvutekij\u00e4reseptori (EGFR) on yhdess\u00e4 kollageeni- ja lamiinireseptori \u03b12\u03b21-integriinin kanssa t\u00e4rke\u00e4 tekij\u00e4 solun selviytymisen, kiinnittymisen ja jakautumisen s\u00e4\u00e4telemisess\u00e4 sek\u00e4 sy\u00f6p\u00e4soluissa.\r\nKasvutekij\u00e4n sitoutumisen j\u00e4lkeen EGFR:t dimerisoituvat, endosytoituvat klatriiniv\u00e4litteisen endosytoosin kautta ja kulkeutuvat solun sis\u00e4ll\u00e4 kolmen eri reitin mukaisesti: 1) EGFR-ligandi-kompleksi voi ubikitinaation seurauksena p\u00e4\u00e4ty\u00e4 lysosomaaliseen pH:sta riippuvaan hajoitukseen, EGFR kierr\u00e4ttyy takaisin solukalvolle 2) ligandin irtoamisen tai 3) UBPY de-ubikitinaatioenstyymin toimesta. \r\n\u03b12\u03b21-integriinireseptori klusteroituu solukalvolle kiinnitytty\u00e4\u00e4n kollageeniin, lamiiniin, Echovirus1:een tai vasta-aineeseen ja endosytoituu ligandistaan riippuen joko klatriini- tai kaveoliini-lipidilauttav\u00e4litteisell\u00e4 endosytoosilla.\r\nProteiinikinaasi C:n (PKC) aktivaatio vaikuttaa sek\u00e4 integriinin, ett\u00e4 EGFR:n endosytoosissa. \u03b12\u03b21-integriinin endosytoosi on riippuvainen PKC\u03b1-aktivaatiosta. EGFR:lla threoniini 654:n fosforylaatio PKC\u03b1:n toimesta est\u00e4\u00e4 reseptorin ubikitinaation ja ohjaa sen kierr\u00e4tt\u00e4v\u00e4lle endosytoottiselle reitille.\r\nAikaisempien tutkimuksiemme mukaan EGFR- ja \u03b12\u03b21-Integriiniendosomit kulkeutuvat solun sis\u00e4ll\u00e4 hyvin l\u00e4hell\u00e4 toisiaan p\u00e4\u00e4tyen lopulta monivesikulaarisiin rakenteisiin. Reseptorit eiv\u00e4t kuitenkaan ole fyysisess\u00e4 kontaktissa ja niiden vesikkelit ovat eri pH:ta. EGFR:n ja Integriinin v\u00e4lill\u00e4 tiedet\u00e4\u00e4n kuitenkin olevan yhteyksi\u00e4 ja \u03b12\u03b21-integriinin kautta tapahtuvan Echovirus1-infektion on havaittu vaikuttavan EGFR-hajotukseen. \r\nT\u00e4ss\u00e4 tutkimuksessa halusimme selvitt\u00e4\u00e4 kuinka EV1-infektio vaikuttaa EGFR-s\u00e4\u00e4telyyn. Keuhkosy\u00f6p\u00e4solulinja A549:n EV1-infektoitujen ja infektoimattomien solujen lyso- tai proteosomaalinen hajotus estettiin bafilomysiiniA:lla, calpainilla tai bortezomibilla. PKC\u03b1:n vaikutusta tutkittaessa kinaasi aktivoitiin phorboli 12-myristaatti 13-asetaatilla. K\u00e4siteltyj\u00e4 soluja kuvattiin konfokaalimikroskoopilla joko pedattuina kaksiulotteisesti tai el\u00e4vin\u00e4 neliulotteisesti. Kvantitatiivinen kuvadata-analyysi tehtiin BioImageXD:ll\u00e4. Kasvutekij\u00e4ll\u00e4 aktivoituja A549-soluja kuvattiin my\u00f6s transmissioelektronimikroskoopilla.\r\nTuloksemme osoittivat ett\u00e4 EGFR kulkeutui koeasetelmassamme samankaltaisten endosomaalisten rakenteiden kautta kuin EV1-\u03b12\u03b21-Integriinikompleksi. EV1-infektio vaikuttaa EGFR-kuljetukseen PKC\u03b1-aktivaatiota muistuttavalla tavalla: EGFR ohjautuu kierr\u00e4tt\u00e4v\u00e4lle endosytoosireitille ja sen hajotus heikkenee. Tuloksemme viittaavat EV1-infektion vaikuttavan EGFR:iin juuri PKC\u03b1-aktivaation kautta. EV1-\u03b12\u03b21-integriinikompleksin hajotuksen estyminen n\u00e4ytti my\u00f6s lis\u00e4\u00e4v\u00e4n EGFR:n kertymist\u00e4 solujen sis\u00e4lle, joten viruksen vaikutus EGFR-reittiin v\u00e4littyy viel\u00e4 endosytoosin j\u00e4lkeenkin. N\u00e4m\u00e4 tulokset ovat yhdenmukaisia aikaisemmin tehtyjen havaintojen kanssa, joiden mukaan \u03b12\u03b21-integriinin ja EGFR:n v\u00e4lill\u00e4 on selv\u00e4, vaikkakaan ei fyysinen, vuorovaikutus. On hyvin mahdollista ett\u00e4 EV1 hy\u00f6tyy EGFR:-hajotuksen hidastamisesta. Virukselle on hy\u00f6dyllist\u00e4 pitkitt\u00e4\u00e4 EGFR:n solunsis\u00e4ist\u00e4 signalointia, joka s\u00e4\u00e4telee Ras-ERK-signalointisarjan kautta mitogeneesi\u00e4 ja PI3-Akt-signalointireitin kautta johtaa anti-apoptoottiseen signalointiin. Molempien signalointireittien s\u00e4\u00e4tely mahdollistaa virukselle paremmat solunsis\u00e4iset replikaatio-olosuhteet.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Alongside with collagen and lamin receptor \u03b12\u03b21-Integrin, epidermal growth factor receptor (EGFR) is a crucial factor in cell survival, attachment, proliferation, mitosis and metastasis formation. Growth factor attachment dimerizes EGFRs which in turn induces clathrin dependent endocytosis of the EGFR-Ligand complex. EGFR has three distinct pathways within the cell: 1) EGFR-ligand complex undergoes lysosomal pH-dependent degradation by ubiquitination or gets recycled back to the cell surface through 2) ligand detachment or 3) UBPY de-ubiquitination enzyme.\r\n\u03b12\u03b21-Integrin clusters on cellular membrane after collagen, lamin, Echovirus1 or antibody attachment and gets endocytosed, depending on the ligand, either by clathrin or caveolae-lipidraft dependent endocytosis.\r\nProteinkinase C (PKC) activation affects both integrin and EGFR endocytosis. \u03b12\u03b21-Integrin endocytosis is dependant on PKC \u03b1 activation. Phosphorylation of EGFR threonine 654 by PKC \u03b1 inhibits receptor ubiquitination and directs it to recyclive endosomal route.\r\nOur previous studies show close proximity between the EGFR and \u03b12\u03b21-Integrin endosomes as they get transported by intracellular pathways but these endosomes vary in pH and have no physical contact. EGFR and Integrin pathways have also been shown to be intertwined together and EV1 Infection through \u03b12\u03b21-Integrin is shown to affect EGFR-degradation.\r\nThe goal of this study was to illustrate how EV1 infection modifies EGFR-regulation. Lyso- and proteosomal degradation in EV1 infected and uninfected A549 pulmonary cancer cells was inhibited by bafilomycinA, calpain or bortezomib. PKC \u03b1 studies were performed by activating the kinase with phorbol 12-myristate 13-acetate. Treated cells were imaged with confocal microscope by 2D-imaging of fixed samples or 4D-imaging of live samples. Quantitative image analysis was performed with the BioImageXD image software. Growth factor activated cells were also imaged by transmission electron microscope.\r\nOur results show that in our laboratory model EGFR was transported through endosomal structures similar to the transport of EV1- \u03b12\u03b21-Integrin complex. EV1 was shown to affect EGFR transport with resemblance to PKC\u03b1 activation: EGFR is directed to recyclive endosomal pathway with reduced receptor degradation. Further studies indicated that these results were indeed due to PKC\u03b1 activation by EV1. The Inhibition of EV1- \u03b12\u03b21-Integrin complex degradation seemed to result in cytoplasmic EGFR accumulation proving that EV1 retains its effects on EGFR pathway also after the endocytosis. These results are consistent with the previous findings that show interplay between the \u03b12\u03b21-Integrin and EGFR. It\u2019s very likely that down regulation of EGFR degradation is beneficial to EV1: Prolonged intracellular signaling by EGFR that regulates mitogenesis through PI3-Akt and Ras-ERK-signaling cascade results in anti-apoptotic signaling. Regulation of these two pathways enables favorable and better conditions for the EV1\u2019s intracellular replication.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Ilari Kuronen (ilsakuro) on 2014-04-28 13:58:50.954759. Form: Pro gradu -lomake (1 tekij\u00e4) (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake-1-tekijae). JyX data:", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by jyx lomake-julkaisija (jyx-julkaisija@noreply.fi) on 2014-04-28T13:58:51Z\r\nNo. of bitstreams: 2\r\nURN:NBN:fi:jyu-201404281590.pdf: 1555665 bytes, checksum: dfee6785b86150b97624a93929960eb8 (MD5)\r\nlicense.html: 4936 bytes, checksum: a2af4440eee7c43555b120f47f0c6105 (MD5)", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2014-04-28T13:58:51Z (GMT). No. of bitstreams: 2\r\nURN:NBN:fi:jyu-201404281590.pdf: 1555665 bytes, checksum: dfee6785b86150b97624a93929960eb8 (MD5)\r\nlicense.html: 4936 bytes, checksum: a2af4440eee7c43555b120f47f0c6105 (MD5)\r\n Previous issue date: 2013", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "1 verkkoaineisto (50 sivua)", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "fin", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "Endosomaalinen kuljetus", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Epidermaalinen kasvutekij\u00e4reseptori", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "alpha2beta1-Integriini", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Echovirus 1", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "Proteiinikinaasi C", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Echovirus 1 infektion vaikutus epidermaalisen kasvutekij\u00e4reseptorin endosytoosiin ja signalointiin", "language": null, "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201404281590", "language": null, "element": "identifier", 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