Salt-inducible kinase-mediated regulation of steroidogenesis at the early stage of ACTH-stimulation
Autor: | Hiroshi Takemori, Nanao Horike, Junko Doi, Xing-zi Lin, Masaaki Muraoka, Yoshiko Katoh, Li Min, Zin-nong Wang, Mitsuhiro Okamoto |
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Rok vydání: | 2003 |
Předmět: |
endocrine system
medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Mutant Chromosomal translocation Adrenocorticotropic hormone Protein Serine-Threonine Kinases CREB Biochemistry Mice Endocrinology Adrenocorticotropic Hormone Internal medicine Gene expression medicine Animals Amino Acid Sequence Molecular Biology Psychological repression Sequence Homology Amino Acid biology Kinase bZIP domain Cell Biology Cyclic AMP-Dependent Protein Kinases Cell biology Kinetics Protein Transport biology.protein Molecular Medicine Steroids Sequence Alignment Signal Transduction |
Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 85:397-400 |
ISSN: | 0960-0760 |
DOI: | 10.1016/s0960-0760(03)00199-7 |
Popis: | Salt-inducible kinase (SIK), expressed in Y1 mouse adrenocortical tumor cells at an early stage of adrenocorticotropic hormone (ACTH)-stimulation, represses the cAMP-responsive element (CRE)-dependent gene expression of CYP11A and StAR by acting on bZIP domain of CRE-binding protein. ACTH induced the SIK’s nuclear to cytosolic translocation in a PKA-dependent manner. A mutant SIK in which the PKA-dependently phosphorylatable Ser577 had been replaced with Ala could not move out of the nucleus. The degree of CRE-reporter repression by SIK was strong as long as SIK was present in the nucleus. These indicated that intracellular translocation of SIK might be an important factor to determine the time-dependent change in the level of steroidogenic gene expression in ACTH-stimulated cells. Promoter analyses suggested that SIK repressed gene expressions not only of CYP11A and StAR but also of CYP11B1, CYP11B2 and SIK itself. We propose here that SIK is one of important molecule regulating expression of steroidogenic genes in the early phase of ACTH treatment. |
Databáze: | OpenAIRE |
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