AKAP SIGNALING AND DISEASE

Most cells typically express 15-20 different AKAPs, thereby creating an archipelago of signaling islands that can simultaneously propagate individual second messenger signaling events. The importance of this local signaling mechanism is underscored by evidence that loss of AKAP-mediated enzyme targeting disrupts essential physiological processes such as learning and memory, cardiac function, and insulin release. For these reasons, the Scott lab has begun to focus on how defective AKAP signaling contributes to disease. We are investigation of mutations in the catalytic subunit of protein kinase A (PKAc) drive the stress hormone disorder adrenal Cushing’s syndrome. We have discovered that displacement of Cushing’s PKA variants from AKAP signaling islands drives the transmission of a distinct pathogenic signals. In a different context we are investigating the impact of DNAJ-PKAc, an oncogenic kinase fusion that contributes to the progression of Fibrolamellar Carcinoma, a devastating adolescent cancer that impacts seemingly healthy individuals between the ages of 15-25.