Salt-inducible kinase-mediated regulation of steroidogenesis at the early stage of ACTH-stimulation.
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.
Takemori
Hiroshi
H
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
Doi
Junko
J
Horike
Nanao
N
Katoh
Yoshiko
Y
Min
Li
L
Lin
Xing-zi
XZ
Wang
Zin-nong
ZN
Muraoka
Masaaki
M
Okamoto
Mitsuhiro
M
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*
D013256:Steroids; D000324:Adrenocorticotropic Hormone; D017346:Protein Serine-Threonine Kinases; C120299:Sik1 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases