BRSK2

BRSK2 is an AMPK-related serine/threonine kinase required with BRSK1/SAD-A for neuronal polarization^[1]. Mechanistically, LKB1 activates SAD/BRSK kinases in a pathway required for axon specification, linking BRSK2-related signaling to neuronal polarity models^[2]. In β-cells, BRSK2 interacts with PCTAIRE1/CDK16 and phosphorylates Ser-12, negatively regulating glucose-stimulated insulin secretion^[3]. In human and mouse metabolic models, β-cell BRSK2 promotes hyperinsulinemia-coupled insulin resistance and associates with type 2 diabetes genetic variants^[4]. In stress and cancer models, BRSK2 suppresses mTORC1, increases Akt activity, and represses NRF2 through reduced protein translation^[5][6]. Compared with related isoforms, BRSK2 shares NRF2-repressive activity with BRSK1, whereas breast cancer data report BRSK1 silencing and BRSK2-linked AKT, STAT3, NF-κB, autophagy, growth, and survival signaling^[6][7]. For experimental applications, GW296115 and BRSK2 siRNA reduced nutrient-deprivation autophagy, cell growth, metastatic potential, and increased apoptosis in breast cancer cells^[7].