This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Han, S.-i.
Right arrow Articles by Kataoka, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Han, S.-i.
Right arrow Articles by Kataoka, K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2007, p. 6593-6605, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.01573-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

MafA Stability in Pancreatic ß Cells Is Regulated by Glucose and Is Dependent on Its Constitutive Phosphorylation at Multiple Sites by Glycogen Synthase Kinase 3{triangledown}

Song-iee Han,{dagger} Shinsaku Aramata, Kunio Yasuda, and Kohsuke Kataoka*

Laboratory of Molecular and Developmental Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma, Japan

Received 23 August 2006/ Returned for modification 22 September 2006/ Accepted 23 July 2007

Regulation of insulin gene expression by glucose in pancreatic ß cells is largely dependent on a cis-regulatory element, termed RIPE3b/C1, in the insulin gene promoter. MafA, a member of the Maf family of basic leucine zipper (bZip) proteins, is a ß-cell-specific transcriptional activator that binds to the C1 element. Based on increased C1-binding activity, MafA protein levels appear to be up-regulated in response to glucose, but the underlying molecular mechanism for this is not well understood. In this study, we show evidence supporting that the amino-terminal region of MafA is phosphorylated at multiple sites by glycogen synthase kinase 3 (GSK3) in ß cells. Mutational analysis of MafA and pharmacological inhibition of GSK3 in MIN6 ß cells strongly suggest that the rate of MafA protein degradation is regulated by glucose, that MafA is constitutively phosphorylated by GSK3, and that phosphorylation is a prerequisite for rapid degradation of MafA under low-glucose conditions. Our data suggest a new glucose-sensing signaling pathway in islet ß cells that regulates insulin gene expression through the regulation of MafA protein stability.

* Corresponding author. Mailing address: Laboratory of Molecular and Developmental Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma 630-0192, Japan. Phone: 81-743-72-5551. Fax: 81-743-72-5559. E-mail: kkataoka{at}bs.naist.jp

{triangledown} Published ahead of print on 6 August 2007.

{dagger} Present address: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.

Molecular and Cellular Biology, October 2007, p. 6593-6605, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.01573-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Harmon, J. S., Bogdani, M., Parazzoli, S. D., Mak, S. S. M., Oseid, E. A., Berghmans, M., LeBoeuf, R. C., Robertson, R. P. (2009). {beta}-Cell-Specific Overexpression of Glutathione Peroxidase Preserves Intranuclear MafA and Reverses Diabetes in db/db Mice. Endocrinology 150: 4855-4862 [Abstract] [Full Text]  
  • Kondo, T., Khattabi, I. E., Nishimura, W., Laybutt, D. R., Geraldes, P., Shah, S., King, G., Bonner-Weir, S., Weir, G., Sharma, A. (2009). p38 MAPK Is a Major Regulator of MafA Protein Stability under Oxidative Stress. Mol. Endocrinol. 23: 1281-1290 [Abstract] [Full Text]  
  • Shao, C., Cobb, M. H. (2009). Sumoylation Regulates the Transcriptional Activity of MafA in Pancreatic {beta} Cells. J. Biol. Chem. 284: 3117-3124 [Abstract] [Full Text]  
  • Guo, S., Burnette, R., Zhao, L., Vanderford, N. L., Poitout, V., Hagman, D. K., Henderson, E., Ozcan, S., Wadzinski, B. E., Stein, R. (2009). The Stability and Transactivation Potential of the Mammalian MafA Transcription Factor Are Regulated by Serine 65 Phosphorylation. J. Biol. Chem. 284: 759-765 [Abstract] [Full Text]  
  • Martin, C. C, Flemming, B. P, Wang, Y., Oeser, J. K, O'Brien, R. M (2008). Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. J Mol Endocrinol 41: 315-328 [Abstract] [Full Text]  
  • Vanhoose, A. M., Samaras, S., Artner, I., Henderson, E., Hang, Y., Stein, R. (2008). MafA and MafB Regulate Pdx1 Transcription through the Area II Control Region in Pancreatic {beta} Cells. J. Biol. Chem. 283: 22612-22619 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»