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.
AuthorsHiroshi Takemori, Junko Doi, Nanao Horike, Yoshiko Katoh, Li Min, Xing-zi Lin, Zin-nong Wang, Masaaki Muraoka, Mitsuhiro Okamoto
JournalThe Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 85 Issue 2-5 Pg. 397-400 (Jun 2003) ISSN: 0960-0760 [Print] England
PMID12943728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Steroids
  • Adrenocorticotropic Hormone
  • Protein-Serine-Threonine Kinases
  • Sik1 protein, rat
  • Cyclic AMP-Dependent Protein Kinases
  • Adrenocorticotropic Hormone (pharmacology)
  • Amino Acid Sequence
  • Animals
  • Cyclic AMP-Dependent Protein Kinases (metabolism)
  • Kinetics
  • Mice
  • Protein Transport
  • Protein-Serine-Threonine Kinases (chemistry, metabolism)
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction (physiology)
  • Steroids (biosynthesis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: