Regulation of CREB-mediated gene expression by salt inducible kinase.
Salt inducible kinase (SIK) was identified as a molecule induced in the adrenal glands of rats fed with a high-salt diet. A major downstream of SIK is regulation of camp-responsive element (CRE)-dependent gene expression. SIK represses the activity of CRE-binding protein (CREB) by phosphorylating a CREB-specific co-activator transducer of regulated CREB activity (TORC). When TORC is dephosphorylated it activates CREB in a CREB-phosphorylation independent manner. The importance of the dephosphorylation of TORC has been suggested by the fact that a kinase inhibitor staurosporine induces dephosphorylation of TORC and upregulates the gene expression of CYP11A, CYP11B1, CYP11B2 and StAR in adrenocortical cells. The identification of SIK caused a stir in the field of CREB studies and led to disclosure of cascades hidden behind the classical mechanism for CREB activity.
Takemori
Hiroshi
H
Laboratory of Cell Signaling and Metabolism, National Institute of Biomedical Innovation, 7-6-8 Asagi, Saito, Ibaraki, Osaka, Japan. takemori@nibio.go.jp
Okamoto
Mitsuhiro
M
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D014157:Transcription Factors / Q000502:physiology
C519510:Crtc1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; C120299:Sik1 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases