dc.contributor.author | Hein, JB | |
dc.contributor.author | Nguyen, HT | |
dc.contributor.author | Garvanska, DH | |
dc.contributor.author | Nasa, I | |
dc.contributor.author | Kruse, T | |
dc.contributor.author | Feng, Y | |
dc.contributor.author | Lopez Mendez, B | |
dc.contributor.author | Davey, N | |
dc.contributor.author | Kettenbach, AN | |
dc.contributor.author | Fordyce, PM | |
dc.contributor.author | Nilsson, J | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-01-30T10:39:56Z | |
dc.date.available | 2024-01-30T10:39:56Z | |
dc.date.issued | 2023-12-06 | |
dc.identifier.citation | Molecular Systems Biology, 2023, 19 (12), pp. e11782 - | |
dc.identifier.issn | 1744-4292 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6136 | |
dc.identifier.eissn | 1744-4292 | |
dc.identifier.eissn | 1744-4292 | |
dc.identifier.doi | 10.15252/msb.202311782 | |
dc.identifier.doi | 10.15252/msb.202311782 | |
dc.description.abstract | Phosphoprotein phosphatases (PPPs) regulate major signaling pathways, but the determinants of phosphatase specificity are poorly understood. This is because methods to investigate this at scale are lacking. Here, we develop a novel in vitro assay, MRBLE:Dephos, that allows multiplexing of dephosphorylation reactions to determine phosphatase preferences. Using MRBLE:Dephos, we establish amino acid preferences of the residues surrounding the dephosphorylation site for PP1 and PP2A-B55, which reveals common and unique preferences. To compare the MRBLE:Dephos results to cellular substrates, we focused on mitotic exit that requires extensive dephosphorylation by PP1 and PP2A-B55. We use specific inhibition of PP1 and PP2A-B55 in mitotic exit lysates coupled with phosphoproteomics to identify more than 2,000 regulated sites. Importantly, the sites dephosphorylated during mitotic exit reveal key signatures that are consistent with MRBLE:Dephos. Furthermore, integration of our phosphoproteomic data with mitotic interactomes of PP1 and PP2A-B55 provides insight into how binding of phosphatases to substrates shapes dephosphorylation. Collectively, we develop novel approaches to investigate protein phosphatases that provide insight into mitotic exit regulation. | |
dc.format | Print-Electronic | |
dc.format.extent | e11782 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGERNATURE | |
dc.relation.ispartof | Molecular Systems Biology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | MRBLE-Pep | |
dc.subject | MRBLE:Dephos | |
dc.subject | mitotic exit | |
dc.subject | protein phosphatase | |
dc.subject | substrates | |
dc.subject | Phosphorylation | |
dc.subject | Protein Phosphatase 2 | |
dc.subject | Mitosis | |
dc.subject | Signal Transduction | |
dc.subject | Substrate Specificity | |
dc.title | Phosphatase specificity principles uncovered by MRBLE:Dephos and global substrate identification. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-10-16 | |
dc.date.updated | 2024-01-30T10:39:14Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.15252/msb.202311782 | |
rioxxterms.licenseref.startdate | 2023-12-06 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37916966 | |
pubs.issue | 12 | |
pubs.organisational-group | ICR | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.15252/msb.202311782 | |
pubs.volume | 19 | |
icr.researchteam | Short Linear Motif | |
dc.contributor.icrauthor | Davey, Norman | |
icr.provenance | Deposited by Mr Arek Surman on 2024-01-30. Deposit type is initial. No. of files: 1. Files: Phosphatase specificity principles uncovered by MRBLEDephos and global substrate identification.pdf | |