Fibrolamellar carcinoma (FLC) is a rare adolescent liver cancer with unique molecular features. FLC emanates from a genetic lesion on chromosome 19 that generates a de novo fusion gene product consisting of the chaperonin-binding domain of Hsp40 (DNAJ), and the catalytic subunit of PKA. Recent work in the Scott lab has found that this chimeric...
A positive prognosis for breast cancer is less certain when primary tumors metastasize. Many signaling pathways that converge on mitochondrial function are engaged during metastasis. Through screening of deidentified cancer patient databases we have detected an inverse relationship between the expression of outer mitochondrial membrane associated anchoring protein dAKAP1 and breast cancer. Genetic depletion of...
Mitch Omar and Tyler Lakey Mutations in the catalytic subunit of protein kinase A (PKAc) drive the stress hormone disorder adrenal Cushing’s syndrome. We define mechanisms of action for the PKAc-L205R and W196R variants. Proximity proteomic techniques demonstrate that both Cushing’s mutants are excluded from A kinase anchoring protein (AKAP) signaling islands, whereas live-cell photoactivation...
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...
