Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets

Files in This Item:
File Description SizeFormat 
RG2-accepted.pdf2.22 MBAdobe PDFDownload
Title: Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets
Authors: Schultess, Jan
Danielewski, Oliver
Smolenski, Albert P.
Permanent link: http://hdl.handle.net/10197/5867
Date: 15-Apr-2005
Online since: 2014-09-16T08:45:32Z
Abstract: The Ras-like guanine-nucleotide-binding protein Rap1 controls integrin alpha(IIb)beta3 activity and platelet aggregation. Recently, we have found that Rap1 activation can be blocked by the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway by type 1 cGMP-dependent protein kinase (cGKI). In search of possible targets of NO/cGMP/cGKI, we studied the expression of Rap1-specific GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs) in platelets. We could detect mRNAs for a new protein most closely related to Rap1GAP and for postsynaptic density-95 discs-large and zona occludens protein 1 (PDZ)-GEF1 and CalDAG-GEFs I and III. Using 5'-rapid amplification of cDNA ends (RACE), we isolated the complete cDNA of the new GAP encoding a 715-amino acid protein, which we have termed Rap1GAP2. Rap1GAP2 is expressed in at least 3 splice variants, 2 of which are detectable in platelets. Endogenous Rap1GAP2 protein partially colocalizes with Rap1 in human platelets. In transfected cells, we show that Rap1GAP2 exhibits strong GTPase-stimulating activity toward Rap1. Rap1GAP2 is highly phosphorylated, and we have identified cGKI as a Rap1GAP2 kinase. cGKI phosphorylates Rap1GAP2 exclusively on serine 7, a residue present only in the platelet splice variants of Rap1GAP2. Phosphorylation of Rap1GAP2 by cGKI might mediate inhibitory effects of NO/cGMP on Rap1. Rap1GAP2 is the first GTPase-activating protein of Rap1 found in platelets and is likely to have an important regulatory role in platelet aggregation.
Type of material: Journal Article
Publisher: American Society of Hematology
Journal: Blood
Volume: 105
Issue: 8
Start page: 3185
End page: 3192
Copyright (published version): 2005 American Society of Hematology
Keywords: Rap1GAP2Platelet aggregation
DOI: 10.1182/blood-2004-09-3605
Language: en
Status of Item: Peer reviewed
Appears in Collections:Medicine Research Collection

Show full item record

Citations 5

Last Week
Last month
checked on Feb 11, 2019

Page view(s) 50

checked on May 25, 2018

Download(s) 50

checked on May 25, 2018

Google ScholarTM



This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.