{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yeung E"],"funding":["Hertz Foundation","National Institutes of Health","Royal Society","NIGMS NIH HHS","National Science Foundation","Engineering and Physical Sciences Research Council"],"pagination":["877-882.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7085240"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(5)"],"pubmed_abstract":["Multisite protein phosphorylation plays a critical role in cell regulation [1-3]. It is widely appreciated that the functional capabilities of multisite phosphorylation depend on the order and kinetics of phosphorylation steps, but kinetic aspects of multisite phosphorylation remain poorly understood [4-6]. Here, we focus on what appears to be the simplest scenario, when a protein is phosphorylated on only two sites in a strict, well-defined order. This scenario describes the activation of ERK, a highly conserved cell-signaling enzyme. We use Bayesian parameter inference in a structurally identifiable kinetic model to dissect dual phosphorylation of ERK by MEK, a kinase that is mutated in a large number of human diseases [7-12]. Our results reveal how enzyme processivity and efficiencies o"],"journal":["Current biology : CB"],"pubmed_title":["Inference of Multisite Phosphorylation Rate Constants and Their Modulation by Pathogenic Mutations."],"pmcid":["PMC7085240"],"funding_grant_id":["EP/R005125/1","R01 GM086537","R35 GM128813","EP/K041096/1","T32 GM007388","EP/R018472/1"],"pubmed_authors":["Shvartsman SY","Filippi S","Wuhr M","McFann S","Harrington HA","Marsh L","Yeung E","Dufresne E"],"additional_accession":[]},"is_claimable":false,"name":"Inference of Multisite Phosphorylation Rate Constants and Their Modulation by Pathogenic Mutations.","description":"Multisite protein phosphorylation plays a critical role in cell regulation [1-3]. It is widely appreciated that the functional capabilities of multisite phosphorylation depend on the order and kinetics of phosphorylation steps, but kinetic aspects of multisite phosphorylation remain poorly understood [4-6]. Here, we focus on what appears to be the simplest scenario, when a protein is phosphorylated on only two sites in a strict, well-defined order. This scenario describes the activation of ERK, a highly conserved cell-signaling enzyme. We use Bayesian parameter inference in a structurally identifiable kinetic model to dissect dual phosphorylation of ERK by MEK, a kinase that is mutated in a large number of human diseases [7-12]. Our results reveal how enzyme processivity and efficiencies o","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Mar","modification":"2026-05-02T14:42:16.65Z","creation":"2021-03-11T08:19:20Z"},"accession":"S-EPMC7085240","cross_references":{"pubmed":["32059766"],"doi":["10.1016/j.cub.2019.12.052"]}}