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
Smolenski, Albert P.
|Permanent link:||http://hdl.handle.net/10197/5865||Date:||25-Jan-2008||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||Copyright (published version):||2008 American Society for Biochemistry and Molecular Biology||Keywords:||Rap1GAP2;Platelet aggregation;Platelet hemostasis||DOI:||10.1074/jbc.M706825200||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Medicine Research Collection|
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