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http://doi.org/10.25358/openscience-4846Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Kumm, Elena J. | - |
| dc.contributor.author | Pagel, Oliver | - |
| dc.contributor.author | Gambaryan, Stepan | - |
| dc.contributor.author | Walter, Ulrich | - |
| dc.contributor.author | Zahedi, René P. | - |
| dc.contributor.author | Smolenski, Albert | - |
| dc.contributor.author | Jurk, Kerstin | - |
| dc.date.accessioned | 2020-06-10T12:24:21Z | - |
| dc.date.available | 2020-06-10T14:24:21Z | - |
| dc.date.issued | 2020 | - |
| dc.identifier.uri | https://openscience.ub.uni-mainz.de/handle/20.500.12030/4848 | - |
| dc.description.abstract | The cell cycle is controlled by microtubule-associated serine/threonine kinase-like (MASTL), which phosphorylates the cAMP-regulated phosphoproteins 19 (ARPP19) at S62 and 19e/α-endosulfine (ENSA) at S67and converts them into protein phosphatase 2A (PP2A) inhibitors. Based on initial proteomic data, we hypothesized that the MASTL-ENSA/ARPP19-PP2A pathway, unknown until now in platelets, is regulated and functional in these anucleate cells. We detected ENSA, ARPP19 and various PP2A subunits (including seven different PP2A B-subunits) in proteomic studies of human platelets. ENSA-S109/ARPP19–S104 were efficiently phosphorylated in platelets treated with cAMP- (iloprost) and cGMP-elevating (NO donors/riociguat) agents. ENSA-S67/ARPP19-S62 phosphorylations increased following PP2A inhibition by okadaic acid (OA) in intact and lysed platelets indicating the presence of MASTL or a related protein kinase in human platelets. These data were validated with recombinant ENSA/ARPP19 and phospho-mutants using recombinant MASTL, protein kinase A and G. Both ARPP19 phosphorylation sites S62/S104 were dephosphorylated by platelet PP2A, but only S62-phosphorylated ARPP19 acted as PP2A inhibitor. Low-dose OA treatment of platelets caused PP2A inhibition, diminished thrombin-stimulated platelet aggregation and increased phosphorylation of distinct sites of VASP, Akt, p38 and ERK1/2 MAP kinases. In summary, our data establish the entire MASTL(like)–ENSA/ARPP19–PP2A pathway in human platelets and important interactions with the PKA, MAPK and PI3K/Akt systems. Keywords: platelets; serine/threonine protein phosphatases; cyclic AMP; cyclic GMP; ENSA; ARPP19; MAP kinase | en_GB |
| dc.description.sponsorship | DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin | - |
| dc.language.iso | eng | - |
| dc.rights | CC BY | de_DE |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
| dc.subject.ddc | 610 Medizin | de_DE |
| dc.subject.ddc | 610 Medical sciences | en_GB |
| dc.title | The cell cycle checkpoint system MAST(L)-ENSA/ARPP19-PP2A is targeted by cAMP/PKA and cGMP/PKG in anucleate human platelets | en_GB |
| dc.type | Zeitschriftenaufsatz | de_DE |
| dc.identifier.urn | urn:nbn:de:hebis:77-publ-598652 | - |
| dc.identifier.doi | http://doi.org/10.25358/openscience-4846 | - |
| jgu.type.dinitype | article | - |
| jgu.type.version | Published version | en_GB |
| jgu.type.resource | Text | - |
| jgu.organisation.department | FB 04 Medizin | - |
| jgu.organisation.number | 2700 | - |
| jgu.organisation.name | Johannes Gutenberg-Universität Mainz | - |
| jgu.rights.accessrights | openAccess | - |
| jgu.journal.title | Cells | - |
| jgu.journal.volume | 9 | - |
| jgu.journal.issue | 2 | - |
| jgu.pages.alternative | Art. 472 | - |
| jgu.publisher.year | 2020 | - |
| jgu.publisher.name | MDPI | - |
| jgu.publisher.place | Basel | - |
| jgu.publisher.uri | http://dx.doi.org/10.3390/cells9020472 | - |
| jgu.publisher.issn | 2073-4409 | - |
| jgu.organisation.place | Mainz | - |
| jgu.subject.ddccode | 610 | - |
| opus.date.accessioned | 2020-06-10T12:24:21Z | - |
| opus.date.modified | 2020-06-24T10:46:59Z | - |
| opus.date.available | 2020-06-10T14:24:21 | - |
| opus.subject.dfgcode | 00-000 | - |
| opus.organisation.string | FB 04: Medizin: Centrum für Thrombose und Hämostase (CTH) | de_DE |
| opus.identifier.opusid | 59865 | - |
| opus.institute.number | 0463 | - |
| opus.metadataonly | false | - |
| opus.type.contenttype | Keine | de_DE |
| opus.type.contenttype | None | en_GB |
| opus.affiliated | Kumm, Elena J. | - |
| opus.affiliated | Walter, Ulrich | - |
| opus.affiliated | Jurk, Kerstin | - |
| jgu.publisher.doi | 10.3390/cells9020472 | |
| jgu.organisation.ror | https://ror.org/023b0x485 | |
| Appears in collections: | JGU-Publikationen | |
