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dc.contributor.authorAu, AE-L
dc.contributor.authorSashindranath, M
dc.contributor.authorBorg, RJ
dc.contributor.authorKleifeld, O
dc.contributor.authorAndrews, RK
dc.contributor.authorGardiner, EE
dc.contributor.authorMedcalf, RL
dc.contributor.authorSamson, AL
dc.date.accessioned2020-12-18T04:30:16Z
dc.date.available2020-12-18T04:30:16Z
dc.date.issued2014-09-11
dc.identifierpii: cddis2014373
dc.identifier.citationAu, A. E. -L., Sashindranath, M., Borg, R. J., Kleifeld, O., Andrews, R. K., Gardiner, E. E., Medcalf, R. L. & Samson, A. L. (2014). Activated platelets rescue apoptotic cells via paracrine activation of EGFR and DNA-dependent protein kinase.. Cell Death Dis, 5 (9), pp.e1410-. https://doi.org/10.1038/cddis.2014.373.
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/11343/256222
dc.description.abstractPlatelet activation is a frontline response to injury, not only essential for clot formation but also important for tissue repair. Indeed, the reparative influence of platelets has long been exploited therapeutically where application of platelet concentrates expedites wound recovery. Despite this, the mechanisms of platelet-triggered cytoprotection are poorly understood. Here, we show that activated platelets accumulate in the brain to exceptionally high levels following injury and release factors that potently protect neurons from apoptosis. Kinomic microarray and subsequent kinase inhibitor studies showed that platelet-based neuroprotection relies upon paracrine activation of the epidermal growth factor receptor (EGFR) and downstream DNA-dependent protein kinase (DNA-PK). This same anti-apoptotic cascade stimulated by activated platelets also provided chemo-resistance to several cancer cell types. Surprisingly, deep proteomic profiling of the platelet releasate failed to identify any known EGFR ligand, indicating that activated platelets release an atypical activator of the EGFR. This study is the first to formally associate platelet activation to EGFR/DNA-PK--an endogenous cytoprotective cascade.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.titleActivated platelets rescue apoptotic cells via paracrine activation of EGFR and DNA-dependent protein kinase.
dc.typeJournal Article
dc.identifier.doi10.1038/cddis.2014.373
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleCell Death and Disease
melbourne.source.volume5
melbourne.source.issue9
melbourne.source.pagese1410-
dc.rights.licenseCC BY
melbourne.elementsid1316533
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540201
melbourne.contributor.authorAu, Amanda
dc.identifier.eissn2041-4889
melbourne.accessrightsOpen Access


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