Figure 8.

Model of AA-regulated signal transduction pathways. An AA-triggered Ca²⁺- ASK1 - p38 pathway induces a transcriptional stress response and mediates HSP27 phosphorylation, thereby contributing to actin filament reorganization in concert with AA-regulated RhoGEFs and RhoGAPs. Other protein kinases phosphorylated in response to AA, such MAP4K2, may also impinge on this pathway. ROS produced by different mechanisms may contribute to p38 phosphorylation to a minor extent in a subset of donors. Orange: phosphosites identified by MS and confirmed by immunoblotting; yellow: phosphosites identified by MS. EX: extracellular space; PM: plasma membrane; CYT: cytosol; NUC: nucleus. AA is most likely derived from extracellular phospholipids with PLA2G2A possibly playing a crucial role (see text and Table 1).