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STRAD pseudokinases regulate axogenesis and LKB1 stability.


ABSTRACT: Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) ? and ?. The roles of STRAD? and STRAD? in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions.We find that STRAD? is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRAD?, whereby STRAD? specifically maintains LKB1 protein levels via cytoplasmic compartmentalization.We demonstrate a novel role for STRAD? in axogenesis and also show for the first time in vivo that STRAD?, but not STRAD?, is responsible for LKB1 protein stability.

SUBMITTER: Veleva-Rotse BO 

PROVIDER: S-EPMC4016016 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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<h4>Background</h4>Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they  ...[more]

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