FIGURE 3:

Phosphoproteome analyses implicate activation of RhoA and Rac-PAK1 signaling and subsequent cytoskeletal remodeling upon stretch. (A) Schematic illustration of the timeline of the phosphoproteome analyses. (B) Heat map and Euclidean distance-based clustering of differentially phosphorylated proteins at 30 min (left panel) and 60 min (right panel) of stretch. At 30 min, 185 up-regulated and 193 down-regulated phosphorylations are detected, and at 60 min, 86 up-regulated and 190 down-regulated phosphorylations are detected. (C) Protein–protein interaction network analysis (STRING) of differentially phosphorylated proteins at 30 min. Various components of the Rho A (purple) and Rac-Pak (magenta) signaling pathways as well as cytoskeletal and cell–-cell adhesion regulators (dark blue) are identified. (D) GO term enrichment analyses of differentially phosphorylated proteins show enrichment of components and regulators of cell–cell adhesions both at 30 and 60 min. In addition, cytoskeletal organization and small GTPases are enriched at 30 min, whereas mRNA splicing is enriched at 60 min. (E) Protein–protein interaction network analysis of differentially phosphorylated proteins at 60 min. Various components of the Rac-Pak signaling pathway, cytoskeletal and cell–cell adhesion regulators (all in dark blue), and filamins (magenta) are identified.