Cyclic Nucleotide Dependent Dephosphorylation of Regulator of G-protein Signaling 18 in Human Platelets

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Title: Cyclic Nucleotide Dependent Dephosphorylation of Regulator of G-protein Signaling 18 in Human Platelets
Authors: Gegenbauer, Kristina
Nagy, Zoltan
Smolenski, Albert P.
Permanent link: http://hdl.handle.net/10197/5879
Date: Nov-2013
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.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Public Library of Science
Copyright (published version): 2013 the authors
Keywords: G-protein signaling 18 (RGS18);Gq signaling;Platelets
DOI: 10.1371/journal.pone.0080251
Language: en
Status of Item: Peer reviewed
Appears in Collections:Medicine Research Collection

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