Document Detail

Up-regulation of TRPM6 transcriptional activity by AP-1 in renal epithelial cells.
MedLine Citation:
PMID:  19937979     Owner:  NLM     Status:  MEDLINE    
Transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of magnesium in the kidney. We recently found that TRPM6 expression is up-regulated by EGF, but the regulatory mechanism has not been clear. TRPM6 mRNA was endogenously expressed in HEK293 cells. TRPM6 mRNA expression was increased by EGF, which was inhibited by U0126, an MEK inhibitor. Promoter activity of human TRPM6 was observed in the TRPM6 5'-flanking region from -1,214 to -718. This promoter activity was enhanced by EGF and inhibited by U0126. Three putative AP-1 binding sites were identified within the region of -1,214/-718. The mutation of the putative AP-1 binding site (-741/-736) completely inhibited the EGF-induced promoter activity. EGF increased p-ERK1/2, c-Fos, c-Jun, and p-c-Jun levels, which were inhibited by U0126. The introduction of c-Fos or c-Jun siRNA inhibited the EGF-induced promoter activity. A chromatin immunoprecipitation assay revealed that c-Fos and c-Jun bind to the AP-1 binding site within the region of -1,214/-718. These results suggest that EGF up-regulates TRPM6 mRNA expression mediate via the activation of ERK/AP-1-dependent pathway.
Akira Ikari; Ayumi Sanada; Chiaki Okude; Hayato Sawada; Yasuhiro Yamazaki; Junko Sugatani; Masao Miwa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  222     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-01-04     Completed Date:  2010-01-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-7     Citation Subset:  IM    
Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Shizuoka, Japan.
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MeSH Terms
5' Flanking Region
Base Sequence
Binding Sites
Butadienes / pharmacology
Cell Line
Epidermal Growth Factor / metabolism*
Epithelial Cells / drug effects,  enzymology,  metabolism*
Kidney / drug effects,  enzymology,  metabolism*
MAP Kinase Kinase Kinases / antagonists & inhibitors,  metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Molecular Sequence Data
Nitriles / pharmacology
Promoter Regions, Genetic
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
RNA Interference
RNA, Messenger / metabolism
Rats, Wistar
TRPM Cation Channels / genetics,  metabolism*
Transcription Factor AP-1 / genetics,  metabolism*
Transcriptional Activation* / drug effects
Reg. No./Substance:
0/Butadienes; 0/Nitriles; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/TRPM Cation Channels; 0/TRPM6 protein, human; 0/TRPM6 protein, rat; 0/Transcription Factor AP-1; 0/U 0126; 62229-50-9/Epidermal Growth Factor; EC Protein Kinase 1; EC Protein Kinase 3; EC Kinase Kinase Kinases

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