A detailed proteomic analysis of rhodocytin-activated platelets reveals novel clues on the CLEC-2 signalosome: Implications for CLEC-2 signaling regulation
| Autor: | Fernández Parguiña, Andrés, Alonso Lorenzo, Jana, Rosa Benito, Isaac, Velez, P, González López, María, Guitian, E, Ebble, J A, Loza García, María Isabel, García Alonso, Ángel |
|---|---|
| Rok vydání: | 2012 |
| Zdroj: | RUNA. Repositorio da Consellería de Sanidade e Sergas Servizo Galego de Saúde (SERGAS) |
| Popis: | C-type lectin-like receptor 2 (CLEC-2) is an essential platelet-activating receptor in hemostasis and thrombosis that is activated by the snake venom rhodocytin. We present here a differential proteomic analysis of basal and rhodocytin-activated platelets with the aim of providing novel clues on CLEC-2 signaling regulation. Proteome analysis was based on 2D-DIGE, phosphotyrosine immunoprecipitations followed by 1D SDS-PAGE and mass spectrometry. Protein-protein interactions were studied by coimmunoprecipitations and a systems biology approach. Overall, we identified 132 proteins differentially regulated after CLEC-2 platelet activation, including most of the major players reported so far in the signaling cascade. In addition, we identified various proteins not previously known to participate in CLEC-2 signaling, such as the adapters Dok-2 and ADAP, tyrosine kinase Fer, and tyrosine phosphatase SHIP-1. We also report an increased association between Dok-2 and SHIP-1 in rhodocytin-stimulated platelets, which might negatively regulate CLEC-2 signaling. Moreover, we also present a comparative analysis of proteomic data for CLEC-2 and glycoprotein VI signaling. We think that our data provide thrombosis-relevant information on CLEC-2 signaling regulation, contributing to a better understanding of this important signaling cascade. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|