Cyclic nucleotide-dependent Protein Kinases Inhibit Binding of 14-3-3 to the GTPase-activating Protein Rap1GAP2 in Platelets

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Title: Cyclic nucleotide-dependent Protein Kinases Inhibit Binding of 14-3-3 to the GTPase-activating Protein Rap1GAP2 in Platelets
Authors: Hoffmeister, Meike
Riha, Pavel
Neumüller, Olga
Smolenski, Albert P.
et al.
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Date: 25-Jan-2008
Online since: 2014-09-16T08:23:33Z
Abstract: GTPase-activating proteins are required to terminate signaling by Rap1, a small guanine nucleotide-binding protein that controls integrin activity and cell adhesion. Recently, we identified Rap1GAP2, a GTPase-activating protein of Rap1 in platelets. Here we show that 14-3-3 proteins interact with phosphorylated serine 9 at the N terminus of Rap1GAP2. Platelet activation by ADP and thrombin enhances serine 9 phosphorylation and increases 14-3-3 binding to endogenous Rap1GAP2. Conversely, inhibition of platelets by endothelium-derived factors nitric oxide and prostacyclin disrupts 14-3-3 binding. These effects are mediated by cGMP- and cAMP-dependent protein kinases that phosphorylate Rap1GAP2 at serine 7, adjacent to the 14-3-3 binding site. 14-3-3 binding does not change the GTPase-activating function of Rap1GAP2 in vitro. However, 14-3-3 binding attenuates Rap1GAP2 mediated inhibition of cell adhesion. Our findings define a novel crossover point of activatory and inhibitory signaling pathways in platelets.
Type of material: Journal Article
Publisher: American Society for Biochemistry and Molecular Biology
Journal: Journal of Biological Chemistry
Volume: 283
Issue: 4
Start page: 2297
End page: 2306
Copyright (published version): 2008 American Society for Biochemistry and Molecular Biology
Keywords: Rap1GAP2Platelet aggregationPlatelet hemostasis
DOI: 10.1074/jbc.M706825200
Language: en
Status of Item: Peer reviewed
Appears in Collections:Medicine Research Collection

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