Fig. 5
From: Disruption of podocyte cytoskeletal biomechanics by dasatinib leads to nephrotoxicity
Phosphoproteomics reveal that processes associated with the actin cytoskeleton are specifically perturbed by dasatinib. a Heatmap for spectral counts of differentially expressed phospho-tyrosine enriched proteins as quantified by LC-MS/MS. Complete list of proteins plotted in the heatmap are shown in Supplementary Table 3. b Enrichment analyses using Wikipathways, KEGG Pathways and other ontology libraries coherently associate focal adhesions and the actin cytoskeleton with the differential phosphoproteome. Highest transcriptional enrichment was for TEAD1 suggesting potential inhibition of the Hippo pathway. c Predicted protein-protein interaction network using the differentially phosphorylated proteins as seed nodes (cyan) and one intermediate neighbor (yellow) is highly interconnected. Node size signifies connectivity. Complete list of network associated proteins and number of connections are listed in Supplementary Table 4. d KINOMEscan analysis reveals that the activity of actin-associated kinases are disproportionately impacted by dasatinib compared to all other tested KIs; in particular LIM kinase (LIMK1) is identified as a kinase that is inhibited exclusively by dasatinib. e Active phosphorylation of kinases from the Rac/Cdc42 pathway (PAK1/2, LIMK1, and cofilin), after treatment with 2 µM KIs for 1 h, show strong, exclusive and statistically significant inhibitory effect for dasatinib but none of the other tested KIs
