Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. / Bouskila, Michale; Hunter, Roger W.; Ibrahim, Adel F.M.; Delattre, Lucie; Peggie, Mark; Van Diepen, Janna A.; Voshol, Peter J.; Jensen, Jørgen; Sakamoto, Kei.

In: Cell Metabolism, Vol. 12, No. 5, 03.11.2010, p. 456-466.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bouskila, M, Hunter, RW, Ibrahim, AFM, Delattre, L, Peggie, M, Van Diepen, JA, Voshol, PJ, Jensen, J & Sakamoto, K 2010, 'Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle', Cell Metabolism, vol. 12, no. 5, pp. 456-466. https://doi.org/10.1016/j.cmet.2010.10.006

APA

Bouskila, M., Hunter, R. W., Ibrahim, A. F. M., Delattre, L., Peggie, M., Van Diepen, J. A., Voshol, P. J., Jensen, J., & Sakamoto, K. (2010). Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. Cell Metabolism, 12(5), 456-466. https://doi.org/10.1016/j.cmet.2010.10.006

Vancouver

Bouskila M, Hunter RW, Ibrahim AFM, Delattre L, Peggie M, Van Diepen JA et al. Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. Cell Metabolism. 2010 Nov 3;12(5):456-466. https://doi.org/10.1016/j.cmet.2010.10.006

Author

Bouskila, Michale ; Hunter, Roger W. ; Ibrahim, Adel F.M. ; Delattre, Lucie ; Peggie, Mark ; Van Diepen, Janna A. ; Voshol, Peter J. ; Jensen, Jørgen ; Sakamoto, Kei. / Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. In: Cell Metabolism. 2010 ; Vol. 12, No. 5. pp. 456-466.

Bibtex

@article{ff5ac053f52f44f49770576ef78d4129,
title = "Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle",
abstract = "Glycogen synthase (GS), a key enzyme in glycogen synthesis, is activated by the allosteric stimulator glucose-6-phosphate (G6P) and by dephosphorylation through inactivation of GS kinase-3 with insulin. The relative importance of these two regulatory mechanisms in controlling GS is not established, mainly due to the complex interplay between multiple phosphorylation sites and allosteric effectors. Here we identify a residue that plays an important role in the allosteric activation of GS by G6P. We generated knockin mice in which wild-type muscle GS was replaced by a mutant that could not be activated by G6P but could still be activated normally by dephosphorylation. We demonstrate that knockin mice expressing the G6P-insensitive mutant display an ∼80% reduced muscle glycogen synthesis by insulin and markedly reduced glycogen levels. Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo.",
author = "Michale Bouskila and Hunter, {Roger W.} and Ibrahim, {Adel F.M.} and Lucie Delattre and Mark Peggie and {Van Diepen}, {Janna A.} and Voshol, {Peter J.} and J{\o}rgen Jensen and Kei Sakamoto",
year = "2010",
month = nov,
day = "3",
doi = "10.1016/j.cmet.2010.10.006",
language = "English",
volume = "12",
pages = "456--466",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle

AU - Bouskila, Michale

AU - Hunter, Roger W.

AU - Ibrahim, Adel F.M.

AU - Delattre, Lucie

AU - Peggie, Mark

AU - Van Diepen, Janna A.

AU - Voshol, Peter J.

AU - Jensen, Jørgen

AU - Sakamoto, Kei

PY - 2010/11/3

Y1 - 2010/11/3

N2 - Glycogen synthase (GS), a key enzyme in glycogen synthesis, is activated by the allosteric stimulator glucose-6-phosphate (G6P) and by dephosphorylation through inactivation of GS kinase-3 with insulin. The relative importance of these two regulatory mechanisms in controlling GS is not established, mainly due to the complex interplay between multiple phosphorylation sites and allosteric effectors. Here we identify a residue that plays an important role in the allosteric activation of GS by G6P. We generated knockin mice in which wild-type muscle GS was replaced by a mutant that could not be activated by G6P but could still be activated normally by dephosphorylation. We demonstrate that knockin mice expressing the G6P-insensitive mutant display an ∼80% reduced muscle glycogen synthesis by insulin and markedly reduced glycogen levels. Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo.

AB - Glycogen synthase (GS), a key enzyme in glycogen synthesis, is activated by the allosteric stimulator glucose-6-phosphate (G6P) and by dephosphorylation through inactivation of GS kinase-3 with insulin. The relative importance of these two regulatory mechanisms in controlling GS is not established, mainly due to the complex interplay between multiple phosphorylation sites and allosteric effectors. Here we identify a residue that plays an important role in the allosteric activation of GS by G6P. We generated knockin mice in which wild-type muscle GS was replaced by a mutant that could not be activated by G6P but could still be activated normally by dephosphorylation. We demonstrate that knockin mice expressing the G6P-insensitive mutant display an ∼80% reduced muscle glycogen synthesis by insulin and markedly reduced glycogen levels. Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo.

UR - http://www.scopus.com/inward/record.url?scp=78049444162&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2010.10.006

DO - 10.1016/j.cmet.2010.10.006

M3 - Journal article

C2 - 21035757

AN - SCOPUS:78049444162

VL - 12

SP - 456

EP - 466

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 5

ER -

ID: 239572706