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dc.contributor.authorClark, K
dc.contributor.authorMiddelbeek, J
dc.contributor.authorMorrice, NA
dc.contributor.authorFigdor, CG
dc.contributor.authorLasonder, Edwin
dc.contributor.authorvan Leeuwen, FN
dc.date.accessioned2016-07-11T15:06:00Z
dc.date.available2016-07-11T15:06:00Z
dc.date.issued2008-03-26
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.otherARTN e1876
dc.identifier.urihttp://hdl.handle.net/10026.1/5048
dc.description.abstract

TRPM6 and TRPM7 are bifunctional proteins expressing a TRP channel fused to an atypical alpha-kinase domain. While the gating properties of TRPM6 and TRPM7 channels have been studied in detail, little is known about the mechanisms regulating kinase activity. Recently, we found that TRPM7 associates with its substrate myosin II via a kinase-dependent mechanism suggesting a role for autophosphorylation in substrate recognition. Here, we demonstrate that the cytosolic C-terminus of TRPM7 undergoes massive autophosphorylation (32+/-4 mol/mol), which strongly increases the rate of substrate phosphorylation. Phosphomapping by mass spectrometry indicates that the majority of autophosphorylation sites (37 out of 46) map to a Ser/Thr-rich region immediately N-terminal of the catalytic domain. Deletion of this region prevents substrate phosphorylation without affecting intrinsic catalytic activity suggesting that the Ser/Thr-rich domain contributes to substrate recognition. Surprisingly, the TRPM6-kinase is regulated by an analogous mechanism despite a lack of sequence conservation with the TRPM7 Ser/Thr-rich domain. In conclusion, our findings support a model where massive autophosphorylation outside the catalytic domain of TRPM6 and TRPM7 may facilitate kinase-substrate interactions leading to enhanced phosphorylation of those substrates.

dc.format.extente1876-e1876
dc.format.mediumElectronic
dc.languageen
dc.language.isoeng
dc.publisherPublic Library of Science (PLoS)
dc.subjectCatalysis
dc.subjectCell Line
dc.subjectHumans
dc.subjectMutagenesis, Site-Directed
dc.subjectMyosin Type II
dc.subjectPhosphorylation
dc.subjectProtein Kinases
dc.subjectProtein Serine-Threonine Kinases
dc.subjectSequence Deletion
dc.subjectSerine
dc.subjectTRPM Cation Channels
dc.subjectThreonine
dc.titleMassive Autophosphorylation of the Ser/Thr-Rich Domain Controls Protein Kinase Activity of TRPM6 and TRPM7
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000260762400027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue3
plymouth.volume3
plymouth.publication-statusPublished online
plymouth.journalPLoS ONE
dc.identifier.doi10.1371/journal.pone.0001876
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
dc.publisher.placeUnited States
dcterms.dateAccepted2008-02-22
dc.identifier.eissn1932-6203
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1371/journal.pone.0001876
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2008-03-26
rioxxterms.typeJournal Article/Review


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