Cyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets.

Hdl Handle:
http://hdl.handle.net/10147/567106
Title:
Cyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets.
Authors:
Gegenbauer, Kristina; Nagy, Zoltan; Smolenski, Albert
Citation:
Cyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets. 2013, 8 (11):e80251 PLoS ONE
Journal:
PloS one
Issue Date:
Nov-2013
URI:
http://hdl.handle.net/10147/567106
DOI:
10.1371/journal.pone.0080251
PubMed ID:
24244663
Additional Links:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080251
Abstract:
Regulator of G-protein signaling 18 (RGS18) is a GTPase-activating protein that turns off Gq signaling in platelets. RGS18 is regulated by binding to the adaptor protein 14-3-3 via phosphorylated serine residues S49 and S218 on RGS18. In this study we confirm that thrombin, thromboxane A2, or ADP stimulate the interaction of RGS18 and 14-3-3 by increasing the phosphorylation of S49. Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. To understand the effect of S216 phosphorylation we studied the phosphorylation kinetics of S49, S216, and S218 using Phos-tag gels and phosphorylation site-specific antibodies in transfected cells and in platelets. Cyclic nucleotide-induced detachment of 14-3-3 from RGS18 coincides initially with double phosphorylation of S216 and S218. This is followed by dephosphorylation of S49 and S218. Dephosphorylation of S49 and S218 might be mediated by protein phosphatase 1 (PP1) which is linked to RGS18 by the regulatory subunit PPP1R9B (spinophilin). We conclude that PKA and PKG induced S216 phosphorylation triggers the dephosphorylation of the 14-3-3 binding sites of RGS18 in platelets.
Item Type:
Article
Language:
en
Keywords:
CELL BIOLOGY; PROTEINS
Local subject classification:
NUCLEOTIDES
MeSH:
14-3-3 Proteins; Cell Line; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP-Dependent Protein Kinases; Humans; Immunoprecipitation; Phosphorylation; RGS Proteins; Signal Transduction
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorGegenbauer, Kristinaen
dc.contributor.authorNagy, Zoltanen
dc.contributor.authorSmolenski, Alberten
dc.date.accessioned2015-08-17T09:19:12Zen
dc.date.available2015-08-17T09:19:12Zen
dc.date.issued2013-11en
dc.identifier.citationCyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets. 2013, 8 (11):e80251 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid24244663en
dc.identifier.doi10.1371/journal.pone.0080251en
dc.identifier.urihttp://hdl.handle.net/10147/567106en
dc.description.abstractRegulator of G-protein signaling 18 (RGS18) is a GTPase-activating protein that turns off Gq signaling in platelets. RGS18 is regulated by binding to the adaptor protein 14-3-3 via phosphorylated serine residues S49 and S218 on RGS18. In this study we confirm that thrombin, thromboxane A2, or ADP stimulate the interaction of RGS18 and 14-3-3 by increasing the phosphorylation of S49. Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. To understand the effect of S216 phosphorylation we studied the phosphorylation kinetics of S49, S216, and S218 using Phos-tag gels and phosphorylation site-specific antibodies in transfected cells and in platelets. Cyclic nucleotide-induced detachment of 14-3-3 from RGS18 coincides initially with double phosphorylation of S216 and S218. This is followed by dephosphorylation of S49 and S218. Dephosphorylation of S49 and S218 might be mediated by protein phosphatase 1 (PP1) which is linked to RGS18 by the regulatory subunit PPP1R9B (spinophilin). We conclude that PKA and PKG induced S216 phosphorylation triggers the dephosphorylation of the 14-3-3 binding sites of RGS18 in platelets.en
dc.language.isoenen
dc.relation.urlhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080251en
dc.rightsArchived with thanks to PloS oneen
dc.subjectCELL BIOLOGYen
dc.subjectPROTEINSen
dc.subject.mesh14-3-3 Proteinsen
dc.subject.meshCell Lineen
dc.subject.meshCyclic AMP-Dependent Protein Kinasesen
dc.subject.meshCyclic GMP-Dependent Protein Kinasesen
dc.subject.meshHumansen
dc.subject.meshImmunoprecipitationen
dc.subject.meshPhosphorylationen
dc.subject.meshRGS Proteinsen
dc.subject.meshSignal Transductionen
dc.subject.otherNUCLEOTIDESen
dc.titleCyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets.en
dc.typeArticleen
dc.identifier.journalPloS oneen
dc.description.fundingSFI Science Foundation Irelanden
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen

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