Publicación: BINDING OF EBP50 TO NOX ORGANIZING SUBUNIT P47(PHOX) IS PIVOTAL TO CELLULAR REACTIVE SPECIES GENERATION AND ALTERED VASCULAR PHENOTYPE
Fecha
2016
Autores
Título de la revista
ISSN de la revista
Título del volumen
Editor
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Resumen
OUR FINDINGS IDENTIFY A PREVIOUSLY UNIDENTIFIED ROLE FOR SCAFFOLDING PROTEIN EZRIN-RADIXIN-MOESIN-BINDING PHOSPHOPROTEIN 50 (EBP50; AKA NHERF1) IN THE ACTIVATION OF NADPH OXIDASES (NOX), A FAMILY OF PROFESSIONAL REACTIVE OXYGEN SPECIES (ROS) PRODUCING ENZYMES IMPLICATED IN NUMEROUS PATHOLOGIES. WE DEMONSTRATE THAT EBP50 IS CRITICAL FOR AGONIST-INDUCED PRODUCTION OF ROS SUPEROXIDE ANION (O2??), AND THAT IT DIRECTLY ASSOCIATES WITH THE NOX ORGANIZING SUBUNIT P47PHOX. EBP50 DELETION ABOLISHES ANGIOTENSIN II-INDUCED CELLULAR HYPERTROPHY AND RESISTANCE ARTERY VASOCONSTRICTION. GIVEN THE WIDE ARRAY OF EBP50 CELLULAR INTERACTIONS AND THE UBIQUITY OF NOX, THE CURRENT FINDINGS SUPPORT A BROADER, MORE COMPLEX ORCHESTRATION OF NOX REGULATION THAN IS CURRENTLY HYPOTHESIZED. THE FINDINGS COULD AUGMENT FUTURE STRATEGIES TARGETING THIS INTERACTION IN DISEASE INVOLVING ABERRANT ROS, TISSUE REMODELING, AND/OR SMOOTH MUSCLE CONSTRICTION.
