PMID- 20876121
OWN - NLM
STAT- MEDLINE
DCOM- 20101122
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 41
DP  - 2010 Oct 12
TI  - Suppressor of MEK null (SMEK)/protein phosphatase 4 catalytic subunit (PP4C) is a 
      key regulator of hepatic gluconeogenesis.
PG  - 17704-9
LID - 10.1073/pnas.1012665107 [doi]
AB  - Fasting promotes hepatic gluconeogenesis to maintain glucose homeostasis. The 
      cAMP-response element binding protein (CREB)-regulated transcriptional 
      coactivator 2 (CRTC2) is responsible for transcriptional activation of 
      gluconeogenic genes and is critical for conveying the opposing hormonal signals 
      of glucagon and insulin in the liver. Here, we show that suppressor of MEK null 1 
      (SMEK1) and SMEK2 [protein phosphatase 4 (PP4) regulatory subunits 3a and 3b, 
      respectively] are directly involved in the regulation of hepatic glucose 
      metabolism in mice. Expression of hepatic SMEK1/2 is up-regulated during fasting 
      or in mouse models of insulin-resistant conditions in a Peroxisome 
      Proliferator-Activated Receptor-gamma Coactivator 1alpha (PGC-1alpha)-dependent manner. 
      Overexpression of SMEK promotes elevations in plasma glucose with increased 
      hepatic gluconeogenic gene expression, whereas depletion of the SMEK proteins 
      reduces hyperglycemia and enhances CRTC2 phosphorylation; the effect is blunted 
      by S171A CRTC2, which is refractory to salt-inducible kinase (SIK)-dependent 
      inhibition. Taken together, we would propose that mammalian SMEK/PP4C proteins 
      are involved in the regulation of hepatic glucose metabolism through 
      dephosphorylation of CRTC2.
FAU - Yoon, Young-Sil
AU  - Yoon YS
AD  - Department of Molecular Cell Biology and Samsung Biomedical Research Institute, 
      Sungkyunkwan University School of Medicine, Gyeonggi-do 440-746, Korea.
FAU - Lee, Min-Woo
AU  - Lee MW
FAU - Ryu, Dongryeol
AU  - Ryu D
FAU - Kim, Jeong Ho
AU  - Kim JH
FAU - Ma, Hui
AU  - Ma H
FAU - Seo, Woo-Young
AU  - Seo WY
FAU - Kim, Yo-Na
AU  - Kim YN
FAU - Kim, Su Sung
AU  - Kim SS
FAU - Lee, Chul Ho
AU  - Lee CH
FAU - Hunter, Tony
AU  - Hunter T
FAU - Choi, Cheol Soo
AU  - Choi CS
FAU - Montminy, Marc R
AU  - Montminy MR
FAU - Koo, Seung-Hoi
AU  - Koo SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100927
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Crtc2 protein, mouse)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Protein Subunits)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (protein phosphatase 4)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Chromatin Immunoprecipitation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation/*physiology
MH  - Gluconeogenesis/*physiology
MH  - Immunoprecipitation
MH  - Liver/metabolism/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Phosphoprotein Phosphatases/*metabolism
MH  - Phosphorylation
MH  - Protein Subunits/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors
PMC - PMC2955085
COIS- The authors declare no conflict of interest.
EDAT- 2010/09/30 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/04/12
CRDT- 2010/09/30 06:00
PHST- 2010/09/30 06:00 [entrez]
PHST- 2010/09/30 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/04/12 00:00 [pmc-release]
AID - 1012665107 [pii]
AID - 201012665 [pii]
AID - 10.1073/pnas.1012665107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17704-9. doi: 
      10.1073/pnas.1012665107. Epub 2010 Sep 27.