Novel Platelet Signalling Pathways Identified via Proteomics

Patricia      B. Maguire; Brian      M. Steele; Desmond      J. Fitzgerald

Abstract

Unbiased proteomic analyses of cell fractions, interactomes and protein modifications coupled with more targeted approaches are adding to an impressive database of the signalling pathways in platelets. In addition to the well characterised receptors that are known to exist on the platelet surface, platelet proteomic studies continue to expose novel transmembrane proteins including CD148, CLEC-2, Eph kinases and Ephrins, Frizzled-4 and -6, G6b, HIP-55, HSP47, LRP5/6 and PEAR-1. In turn identification of novel platelet receptors has led to the discovery of new platelet signalling pathways such as the collagen/CLEC-2 receptor pathway, as well as the canonical WNT pathway. This review focuses on the canonical WNT pathway, providing background information to WNT ligands, receptors and signalling pathways and then focusing on canonical WNT signalling in anucleate platelets, where the suppression of platelet activity and adhesion by its ligand, Wnt-3a has recently been demonstrated.

Keywords: Canonical WNT signalling, frizzled receptors, novel signalling pathways, novel transmembrane proteins, Platelets, β-catenin, Thromboxane, Adenosine diphosphate, Ephrins, mass spectrometry, transmembrane receptor, CLEC-2