FIG. 8.

PSMA-mediated PAK and integrin activation affect endothelial cell function. (A) Hypothetical mechanism for PSMA regulation of endothelial cell invasion. PSMA positively regulates β₁ integrin signaling and PAK phosphorylation in endothelial cells. Because PAK activation/deactivation must be precisely regulated for productive motility, we predict that PAK activation negatively regulates PSMA activity. Therefore, these components constitute a regulatory loop of PSMA regulation in endothelial cells, where β₁ integrin signal trans duction and subsequent PAK activation leads to both productive invasion and downregulation of integrin β₁ signaling via reduction in PSMA activity. (B) Cells transfected with plasmids encoding constitutively active (CA) PAK display increased protrusions in multiple directions. GFP, green fluorescent protein. (C) β₁ activation by the constitutively activating antibody TS2/16 rescues PSMA-dependent invasion in the presence of the PMPA inhibitor. IgG, immunoglobulin G. **, 0.01< P > 0.001. Error bars indicate standard deviations.