PSMA interaction with filamin A in endothelial cells regulates PSMA function. (A) Immunoprecipitation (IP) of PSMA but not immunoglobulin G (IgG) or ICAM-1 pulls down filamin A in HUVECs and filamin, and PSMA colocalizes in migrating HUVECs (PSMA-FITC and filamin-Texas Red [TR] antibodies). Control photobleaching data are provided in Fig. S1 of the supplemental material. (B) PSMA CTD peptide transfection in HUVECs disrupts PSMA/filamin A interaction. Disrupting PSMA/filamin interaction by transfecting the PSMA CTD peptide (C) decreases PSMA enzyme activity (P = 0.003), (D) disrupts endothelial cell morphology, resulting in an increase in membrane protrusions (P < 0.001), (E) decreases endothelial cell invasion (P = 0.002), (F) decreases endothelial cell adhesion to laminin (P = 0.001), and (G) decreases PAK activation as measured by phosphorylated-PAK levels. SCR, scrambled peptides; IB, immunoblot. **, 0.01 < P > 0.001; ***, 0.001 < P > 0.0001. Error bars indicate standard deviations.