PMID- 17682063
OWN - NLM
STAT- MEDLINE
DCOM- 20080122
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 27
IP  - 19
DP  - 2007 Oct
TI  - MafA stability in pancreatic beta cells is regulated by glucose and is dependent 
      on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 
      3.
PG  - 6593-605
AB  - Regulation of insulin gene expression by glucose in pancreatic beta 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 beta-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 beta cells. Mutational analysis of MafA and 
      pharmacological inhibition of GSK3 in MIN6 beta 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 beta cells that regulates insulin 
      gene expression through the regulation of MafA protein stability.
FAU - Han, Song-Iee
AU  - Han SI
AD  - Laboratory of Molecular and Developmental Biology, Graduate School of Biological 
      Science, Nara Institute of Science and Technology, Ikoma, Japan.
FAU - Aramata, Shinsaku
AU  - Aramata S
FAU - Yasuda, Kunio
AU  - Yasuda K
FAU - Kataoka, Kohsuke
AU  - Kataoka K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070806
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (Maf Transcription Factors, Large)
RN  - 0 (Mafa protein, mouse)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - DNA Mutational Analysis
MH  - Enzyme Inhibitors/metabolism
MH  - Gene Expression Regulation
MH  - Glucose/*metabolism
MH  - Insulin/genetics/metabolism
MH  - Insulin-Secreting Cells/cytology/*metabolism
MH  - Maf Transcription Factors, Large/genetics/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Sequence Alignment
MH  - Serine/metabolism
MH  - Signal Transduction/*physiology
MH  - Threonine/metabolism
PMC - PMC2099218
EDAT- 2007/08/08 09:00
MHDA- 2008/01/23 09:00
PMCR- 2008/02/01
CRDT- 2007/08/08 09:00
PHST- 2007/08/08 09:00 [pubmed]
PHST- 2008/01/23 09:00 [medline]
PHST- 2007/08/08 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - MCB.01573-06 [pii]
AID - 1573-06 [pii]
AID - 10.1128/MCB.01573-06 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2007 Oct;27(19):6593-605. doi: 10.1128/MCB.01573-06. Epub 2007 Aug 
      6.