PMID:12200423

Citation	Takemori, H, Katoh, Y, Horike, N, Doi, J and Okamoto, M (2002) ACTH-induced nucleocytoplasmic translocation of salt-inducible kinase. Implication in the protein kinase A-activated gene transcription in mouse adrenocortical tumor cells. J. Biol. Chem. 277:42334-43
Abstract	Salt-inducible kinase (SIK), a serine/threonine protein kinase expressed at an early stage of adrenocorticotropic hormone (ACTH) stimulation in Y1 mouse adrenocortical tumor cells, repressed the cAMP-responsive element (CRE)-dependent gene transcription by acting on the basic leucine zipper domain of the CRE-binding protein (Doi, J., Takemori, H., Lin, X.-z., Horike, N., Katoh, Y., and Okamoto, M. (2002) J. Biol. Chem. 277, 15629-15637). The mechanism of SIK-mediated gene regulation has been further explored. Here we show that SIK changes its subcellular location after the addition of ACTH. The immunocytochemical and fluorocytochemical analyses showed that SIK was present both in the nuclear and cytoplasmic compartments of resting cells; when the cells were stimulated with ACTH the nuclear SIK moved into the cytoplasm within 15 min; the level of SIK in the nuclear compartment gradually returned to the initial level after 12 h. SIK translocation was blocked by pretreatment with leptomycin B. A mutant SIK whose Ser-577, the cAMP-dependent protein kinase (PKA)-dependent phosphorylation site, was replaced with Ala could not move out of the nucleus under stimulation by ACTH. As expected, the degree of repression exerted by SIK on CRE reporter activity was weak as long as SIK was present in the cytoplasmic compartment. The same was true for the SIK-mediated repression of a steroidogenic acute regulatory (StAR) protein-gene promoter, which contained a CRE-like sequence at -95 to -85 bp. These results suggest that in the ACTH-stimulated Y1 cells the nuclear SIK was PKA-dependently phosphorylated, and the phosphorylated SIK was then translocated out of the nuclei. This intracellular translocation of SIK, a CRE-repressor, may account for the time-dependent change in the level of ACTH-activated expression of the StAR protein gene.
Links	PubMed Online version:10.1074/jbc.M204602200
Keywords	Active Transport, Cell Nucleus; Adrenal Cortex Neoplasms/metabolism; Adrenocorticotropic Hormone/pharmacology; Animals; COS Cells; Cyclic AMP Response Element-Binding Protein/chemistry; Cyclic AMP Response Element-Binding Protein/metabolism; Cyclic AMP-Dependent Protein Kinases/physiology; Gene Expression Regulation; Leucine Zippers; Mice; Phosphoproteins/genetics; Phosphorylation; Protein-Serine-Threonine Kinases/metabolism; Response Elements; Transcription, Genetic
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