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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2088-2095.
Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-07-2392.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins
Angel García,
Sripadi Prabhakar,
Sascha Hughan,
Tom W. Anderson,
Chris J. Brock,
Andrew C. Pearce,
Raymond A. Dwek,
Steve P. Watson,
Holger F. Hebestreit, and
Nicole Zitzmann
From the Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom; Department of Pharmacology, University of Oxford, Oxford, United Kingdom; Division of Medical Sciences, The Medical School, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
We have applied a proteomics approach to analyze signaling cascades in human platelets stimulated by thrombin receptor activating peptide (TRAP). By analyzing basal and TRAP-activated platelets using 2-dimensional gel electrophoresis (2-DE), we detected 62 differentially regulated protein features. From these, 41 could be identified by liquid chromatography–coupled tandem mass spectrometry (LC-MS/MS) and were found to derive from 31 different genes, 8 of which had not previously been reported in platelets, including the adapter downstream of tyrosine kinase 2 (Dok-2). Further studies revealed that the change in mobility of Dok-2 was brought about by tyrosine phosphorylation. Dok-2 tyrosine phosphorylation was also found to be involved in collagen receptor, glycoprotein VI (GPVI), signaling as well as in outside-in signaling through the major platelet integrin,  IIb 3. These studies also provided the first demonstration of posttranslational modification of 2 regulator of G protein signaling (RGS) proteins, RGS10 and 18. Phosphorylation of RGS18 was mapped to Ser49 by MS/MS analysis. This study provides a new approach for the identification of novel signaling molecules in activated platelets, providing new insights into the mechanisms of platelet activation and building the basis for the development of therapeutic agents for thrombotic diseases.
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