title: LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons.
abstract: The polarization of axon and dendrites underlies the ability of neurons to integrate and transmit information in the brain. We show here that the serine/threonine kinase LKB1, previously implicated in the establishment of epithelial polarity and control of cell growth, is required for axon specification during neuronal polarization in the mammalian cerebral cortex. LKB1 polarizing activity requires its association with the pseudokinase Stradalpha and phosphorylation by kinases such as PKA and p90RSK, which transduce neurite outgrowth-promoting cues. Once activated, LKB1 phosphorylates and thereby activates SAD-A and SAD-B kinases, which are also required for neuronal polarization in the cerebral cortex. SAD kinases, in turn, phosphorylate effectors such as microtubule-associated proteins that implement polarization. Thus, we provide evidence in vivo and in vitro for a multikinase pathway that links extracellular signals to the intracellular machinery required for axon specification.
authors.affiliation: Neuroscience Center, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Barnes
authors.forename: Brendan N
authors.initials: BN
authors.lastname: Lilley
authors.forename: Y Albert
authors.initials: YA
authors.lastname: Pan
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Plummer
authors.forename: Ashton W
authors.initials: AW
authors.lastname: Powell
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Raines
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
authors.forename: Franck
authors.initials: F
authors.lastname: Polleux
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D016764:Cell Polarity; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C496826:Brsk1 protein, mouse; C496825:Brsk2 protein, mouse; D017346:Protein Serine-Threonine Kinases