Identification of the nuclear localization domain of salt-inducible kinase.
Salt-inducible kinase (SIK), a novel serine/threonine protein kinase from adrenal glands of rats fed with a high-salt diet, is induced by ACTH in Y1 mouse adrenocortical tumor cells. Overexpression of SIK repressed ACTH-mediated expression of CYP11A- and Steroidogenic acute regulatory (StAR)-genes by inhibiting CREB bound to their promoters. Immunocytochemical and GFP-fluorocytochemical analyses indicated that SIK was present both in the nucleus and cytosol of resting cells. Responding to ACTH, the nuclear SIK moved to the cytosol. The level of phosphorylation at Ser577, a canonical PKA-phosphorylation site, was elevated by ACTH treatment. The disruption of the serine residue inhibited the nuclear export and enhanced the transcription repression activity of SIK. Various deletion mutants suggested a functional nuclear localization signal was present near Ser577. We conclude that the nucleocytoplasmic shuttling of SIK may play an important role in the transcriptional regulation of the cAMP-responsive element (CRE)-dependent gene expression.
Katoh
Yoshiko
Y
Department of Molecular Physiological Chemistry, Osaka University Medical School, 2-2 Yamadaoka, Osaka, 565-0871 Japan.
Takemori
Hiroshi
H
Doi
Junko
J
Okamoto
Mitsuhiro
M
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000502:physiology; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D000324:Adrenocorticotropic Hormone; D017346:Protein Serine-Threonine Kinases; C120299:Sik1 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases