Abstract
High NaCl increases TonEBP/OREBP nuclear localization. We find that high NaCl increases phosphorylation of TonEBP/OREBP‐T135, located in its Auxiliary Export Domain (amino acids 132–156). Mutation of T135 to alanine decreases high NaCl‐induced nuclear localization of TonEBP/OREBP. T135 is in a consensus site for phosphorylation by protein kinase CDK5. High NaCl increases phosphorylation of CDK5‐Y15, indicating increased activity. Inhibitors of CDK5 and Kinase Dead (KD) dominant negative CDK5 reduce high NaCl‐induced nuclear localization of TonEBP/OREBP. Furthermore, CDK5 associates with TonEBP/OREBP (coimmunoprecipitation) and directly phosphorylates T135 in vitro. Over expression of CDK5 KD strongly decreases phosphorylation of T135. We do not find any regulation of TonEBP/OREBP transactivating activity by CDK5. We conclude that high NaCl stimulates CDK5 kinase activity which in turn contributes to nuclear localization of TonEBP by phosphorylating it on T135.This research was supported by the Intramural Research Program of NHLBI.
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