Brain-specific kinase 1 (BRSK1; SAD-B) and Brain-specific kinase 2 (BRSK2; SAD-A) are serine/threonine kinases closely related to AMPK. LKB1 phosphorylates Thr189 in the T-loop of BRSK1 and Thr174 in the T-loop of BRSK2, resulting in activation of the kinases (1). BRSK1 localizes to synaptic vesicles in the hippocampus and cerebellum just like the active zone proteins Bassoon and CAST, and BRSK1 phoshorylates the active zone protein RIM1 (2). An alternatively spliced from of BRSK1 has displays unique activity during the cell cycle, phosphorylating Ser131 of gamma-tubulin and controls centrosome duplication (3). Neuronal polariztion, including axon formation, is fundamental for normal brain development. BRSK1 -/- and BRSK2 -/- mice have defects in neuronal polarity and impaired corticogenesis (4). Knockdown of BRSK1 and BRSK2 in vitro diminishes axonal growth (5).
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