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Ppp1r3c  -  protein phosphatase 1, regulatory...

Mus musculus

Synonyms: PP1 subunit R5, PTG, Ppp1r5, Protein phosphatase 1 regulatory subunit 3C, Protein phosphatase 1 regulatory subunit 5, ...
 
 
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Disease relevance of Ppp1r3c

 

Psychiatry related information on Ppp1r3c

  • Following sleep deprivation, a two-fold increase in PTG mRNA and a decrease of mRNAs encoding glycogen synthase and glycogen phosphorylase were observed [5].
 

High impact information on Ppp1r3c

  • A PP1C-targeting protein expressed in 3T3-L1 adipocytes (called PTG, for protein targeting to glycogen) was cloned and characterized [6].
  • Protein targeting to glycogen (PTG) is a scaffolding protein that targets protein phosphatase 1alpha (PP1alpha) to glycogen, and links it to enzymes involved in glycogen synthesis and degradation [1].
  • Insulin resistance in older PTG heterozygous mice correlates with a significant increase in muscle triglyceride content, with a corresponding attenuation of insulin receptor signaling [1].
  • PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance [1].
  • However, PTG knockdown reduced glycogen-targeted PP1 protein levels, corresponding to decreased cellular glycogen synthase- and phosphorylase-directed PP1 activity [2].
 

Chemical compound and disease context of Ppp1r3c

 

Biological context of Ppp1r3c

  • In contrast, glycogenolysis rates were markedly increased, suggesting that PTG primarily acts to suppress glycogen breakdown [2].
  • The effects of PTG seemed specific, because basal and insulin-stimulated phosphorylation of a variety of signaling proteins was unaffected [7].
  • However, very little is known about the metabolic effects of PTG [8].
  • Nuclear extracts prepared from mouse liver and H4IIE cells were able to bind a FoxA2-specific probe derived within the PTG promoter region [4].
  • Induction of PTG mRNA expression was mimicked by the adenylate cyclase activator forskolin and by dibutyryl cAMP, suggesting the involvement of the cAMP-dependent signal transduction cascade [9].
 

Anatomical context of Ppp1r3c

  • We find that overexpression of PTG potently activates glycogen synthesis in cultured hepatocytes [8].
  • PP1-R5/PTG, another glycogen targeted form of PP1, was not significantly stimulated by insulin in the skeletal muscle of WT mice but showed compensatory stimulation by insulin in G(M)(-/-) mice [10].
  • Differentiation of 3T3-L1 fibroblasts into highly insulin-responsive adipocytes resulted in a marked increase in PTG expression [11].
  • In this study, we report the presence of PTG mRNA in adult mouse brain, as well as in astrocytes, a non-neuronal cell type that contains most of brain glycogen [9].
  • We also found that peripheral TNF-alpha level and NK-cell activity were suppressed in the presence of mAbCD28 and its Fab fragments for a relatively long time after PTG transplantation [12].
 

Associations of Ppp1r3c with chemical compounds

  • To investigate the metabolic consequences of altering PTG levels, glucose uptake and storage in 3T3-L1 adipocytes was measured [7].
  • Overexpression of PTG in 3T3-L1 adipocytes using a doxycycline-controllable adenoviral construct resulted in a 10-20-fold increase in PTG levels and an 8-fold increase in glycogen levels [7].
  • The phosphatase activity associated with R3E is slightly higher than that associated with R5/PTG and it is downregulated in streptozotocin-induced diabetes by 60-70% and restored by insulin treatment [13].
  • These data suggest that increased PTG expression by neurotransmitters such as noradrenaline and VIP could represent a major event leading to enhancement of glycogen levels in astrocytes [9].
  • Interestingly, adenosine induces in parallel the expression of the protein targeting to glycogen (PTG), one of the protein phosphatase-1 glycogen-targeting subunits that has been implicated in the control of glycogen levels in various tissues [14].
 

Regulatory relationships of Ppp1r3c

  • Protein targeting to glycogen (PTG) enhances glycogen accumulation by increasing PP1 activity against glycogen-metabolizing enzymes [7].
  • Inclusion of 1 microg/ml doxycycline in the media suppressed PTG expression, and fully reversed all PTG-dependent effects [7].
  • Furthermore, glycogenolytic agents such as forskolin or glucagon are largely ineffective at activating glycogen degradation in PTG overexpressing hepatocytes, even though large increases in cAMP levels are demonstrated [8].
 

Other interactions of Ppp1r3c

 

Analytical, diagnostic and therapeutic context of Ppp1r3c

References

  1. PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance. Crosson, S.M., Khan, A., Printen, J., Pessin, J.E., Saltiel, A.R. J. Clin. Invest. (2003) [Pubmed]
  2. Central role for protein targeting to glycogen in the maintenance of cellular glycogen stores in 3T3-L1 adipocytes. Greenberg, C.C., Danos, A.M., Brady, M.J. Mol. Cell. Biol. (2006) [Pubmed]
  3. Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation. Fernández-Sánchez, M.E., Criado-García, O., Heath, K.E., García-Fojeda, B., Medraño-Fernández, I., Gomez-Garre, P., Sanz, P., Serratosa, J.M., Rodríguez de Córdoba, S. Hum. Mol. Genet. (2003) [Pubmed]
  4. Regulation of the mouse protein targeting to glycogen (PTG) promoter by the FoxA2 forkhead protein and by 3',5'-cyclic adenosine 5'-monophosphate in H4IIE hepatoma cells. Cheng, A., Zhang, M., Crosson, S.M., Bao, Z.Q., Saltiel, A.R. Endocrinology (2006) [Pubmed]
  5. Sleep deprivation modulates brain mRNAs encoding genes of glycogen metabolism. Petit, J.M., Tobler, I., Allaman, I., Borbély, A.A., Magistretti, P.J. Eur. J. Neurosci. (2002) [Pubmed]
  6. PTG, a protein phosphatase 1-binding protein with a role in glycogen metabolism. Printen, J.A., Brady, M.J., Saltiel, A.R. Science (1997) [Pubmed]
  7. Protein targeting to glycogen overexpression results in the specific enhancement of glycogen storage in 3T3-L1 adipocytes. Greenberg, C.C., Meredith, K.N., Yan, L., Brady, M.J. J. Biol. Chem. (2003) [Pubmed]
  8. Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes causes profound activation of glycogen synthesis independent of normal hormone- and substrate-mediated regulatory mechanisms. Berman, H.K., O'Doherty, R.M., Anderson, P., Newgard, C.B. J. Biol. Chem. (1998) [Pubmed]
  9. Protein targeting to glycogen mRNA expression is stimulated by noradrenaline in mouse cortical astrocytes. Allaman, I., Pellerin, L., Magistretti, P.J. Glia (2000) [Pubmed]
  10. Disruption of the striated muscle glycogen targeting subunit PPP1R3A of protein phosphatase 1 leads to increased weight gain, fat deposition, and development of insulin resistance. Delibegovic, M., Armstrong, C.G., Dobbie, L., Watt, P.W., Smith, A.J., Cohen, P.T. Diabetes (2003) [Pubmed]
  11. Role of protein targeting to glycogen (PTG) in the regulation of protein phosphatase-1 activity. Brady, M.J., Printen, J.A., Mastick, C.C., Saltiel, A.R. J. Biol. Chem. (1997) [Pubmed]
  12. CD28/B7-mediated costimulation is required for parathyroid gland allograft rejection in rats. Xiao, Y., Zhu, Y., Chen, L., Wang, S., He, X. Chin. Med. Sci. J. (1999) [Pubmed]
  13. A novel glycogen-targeting subunit of protein phosphatase 1 that is regulated by insulin and shows differential tissue distribution in humans and rodents. Munro, S., Ceulemans, H., Bollen, M., Diplexcito, J., Cohen, P.T. FEBS J. (2005) [Pubmed]
  14. A2B receptor activation promotes glycogen synthesis in astrocytes through modulation of gene expression. Allaman, I., Lengacher, S., Magistretti, P.J., Pellerin, L. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  15. The role of protein phosphatase-1 in insulin action. Brady, M.J., Saltiel, A.R. Recent Prog. Horm. Res. (2001) [Pubmed]
  16. Epinephrine control of glycogen metabolism in glycogen-associated protein phosphatase PP1G/R(GL) knockout mice. Kim, J.H., DePaoli-Roach, A.A. J. Biochem. Mol. Biol. (2002) [Pubmed]
 
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