Figure 6
Figure 6. Case study on integrated network analysis. (A) A graphical representation of the core integrin signaling created by integrating information on phosphorylations, dephosphorylations (green arrows), and interactions (gray lines). Phosphorylations are shown according to the source of detection: red arrows indicate phosphorylations reported from human cells (HPRD), and blue arrows connect platelet proteins with experimentally verified phosphosites and their predicted kinase. The protein nodes are colored according to the source of phosphorylation (red represents phosphorylated in human cells; blue, phosphorylated in platelets; and yellow, a platelet nonphosphorylated protein), and the phosphorylation site is marked on each directed edge. Drugs are visualized with different colors according to the type of drug: investigational (experimental) or approved. DOK1, a docking protein associated with ITGB3 binding, is phosphorylated on Ser269 (highlighted). By further integrating kinase prediction and drug target information, the platelet kinase CLK1 has been proposed, and a putative therapeutic approach using the inhibitor debromohymenialdisine can be suggested. (B) Schematic representation of the DOK1 Ser269 phosphorylation site and the competitive binding between DOK1 and talin for the NPLY motif of the integrin β3-tail. DOK1 binds to the integrin and prevents talin from binding and activating the receptor.

Case study on integrated network analysis. (A) A graphical representation of the core integrin signaling created by integrating information on phosphorylations, dephosphorylations (green arrows), and interactions (gray lines). Phosphorylations are shown according to the source of detection: red arrows indicate phosphorylations reported from human cells (HPRD), and blue arrows connect platelet proteins with experimentally verified phosphosites and their predicted kinase. The protein nodes are colored according to the source of phosphorylation (red represents phosphorylated in human cells; blue, phosphorylated in platelets; and yellow, a platelet nonphosphorylated protein), and the phosphorylation site is marked on each directed edge. Drugs are visualized with different colors according to the type of drug: investigational (experimental) or approved. DOK1, a docking protein associated with ITGB3 binding, is phosphorylated on Ser269 (highlighted). By further integrating kinase prediction and drug target information, the platelet kinase CLK1 has been proposed, and a putative therapeutic approach using the inhibitor debromohymenialdisine can be suggested. (B) Schematic representation of the DOK1 Ser269 phosphorylation site and the competitive binding between DOK1 and talin for the NPLY motif of the integrin β3-tail. DOK1 binds to the integrin and prevents talin from binding and activating the receptor.

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