Fig. 5

The complex signaling network represents the combination of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway Rap1 signaling pathway and Platelet activation (extracted from the KEGG database, hsa04051, hsa04611) related to malonylated proteins in the end-stage renal disease (ESRD) patients when compared to normal controls (NCs). The interaction map comprises the differentially malonylated proteins (green filled red bordered boxes) and were integrated in the regulation of focal adhesion and integrin αIIbβ3 activation. Rap1b-mediated inside-out activation of integrin αIIbβ3 involves the Rap1 effector RIAM and the cytoskeletal proteins talin and kindlin. In turn, integrin αIIbβ3 binding to fibrinogen stimulates an outside-in signaling able to promote Rap1b activation, which is an essential step for platelet spreading on fibrinogen. Malonylated proteins colored in green shades (down-regulation) are enriched in Rap1 signaling pathway and Platelet activation pathway. Abbreviations for the discussed proteins: RAP1: Ras-related protein Rap-1; RIAM: Rap1-interacting adaptor molecule; ADG: diacylglycerol; PLC: phospholipase C; VASP:vasodilator-stimulated phosphoprotein