title: Salt-inducible kinase-mediated regulation of steroidogenesis at the early stage of ACTH-stimulation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medicine (H-1), Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. takemori@mr-mbio.med.osaka-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takemori
authors.forename: Junko
authors.initials: J
authors.lastname: Doi
authors.forename: Nanao
authors.initials: N
authors.lastname: Horike
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Katoh
authors.forename: Li
authors.initials: L
authors.lastname: Min
authors.forename: Xing-zi
authors.initials: XZ
authors.lastname: Lin
authors.forename: Zin-nong
authors.initials: ZN
authors.lastname: Wang
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muraoka
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okamoto
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D013256:Steroids; D000324:Adrenocorticotropic Hormone; D017346:Protein Serine-Threonine Kinases; C120299:Sik1 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases