Cited by 95Metabolism, Diabetes, and CancerCellular transport and secretionProtein Kinase Regulation and GTPase Signaling

Insulin-stimulated Phosphorylation of the Rab GTPase-activating Protein TBC1D1 Regulates GLUT4 Translocation

Open access
Peck, Grantley R., Chavez, Jose A., Roach, William G., Budnik, Bogdan A., Lane, William S., Karlsson, Håkan K.R., Zierath, Juleen R., Lienhard, Gustav E.·2009·Journal of Biological Chemistry

Abstract

Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular locations to the plasma membrane in adipose and muscle cells. Prior studies have shown that Akt phosphorylation of the Rab GTPase-activating protein, AS160 (160-kDa Akt substrate; also known as TBC1D4), triggers GLUT4 translocation, most likely by suppressing its Rab GTPase-activating protein activity. However, the regulation of a very similar protein, TBC1D1 (TBC domain family, member 1), which is mainly found in muscle, in insulin-stimulated GLUT4 translocation has been unclear. In the present study, we have identified likely Akt sites of insulin-stimulated phosphorylation of TBC1D1 in C2C12 myotubes. We show that a mutant of TBC1D1, in which several Akt sites have been converted to alanine, is considerably more inhibitory to insulin-stimulated GLUT4 translocation than wild-type TBC1D1. This result thus indicates that similar to AS160, Akt phosphorylation of TBC1D1 enables GLUT4 translocation. We also show that in addition to Akt activation, activation of the AMP-dependent protein kinase partially relieves the inhibition of GLUT4 translocation by TBC1D1. Finally, we show that the R125W variant of TBC1D1, which has been genetically associated with obesity, is equally inhibitory to insulin-stimulated GLUT4 translocation, as is wild-type TBC1D1, and that healthy and type 2 diabetic individuals express approximately the same level of TBC1D1 in biopsies of vastus lateralis muscle. In conclusion, phosphorylation of TBC1D1 is required for GLUT4 translocation. Thus, the regulation of TBC1D1 resembles that of its paralog, AS160.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/jbc.m109.035568

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TBC1D1 expression is normal in skeletal muscle from type 2 diabetics.

    “TBC1D1 expression is normal in skeletal muscle from type 2 diabetics [99], suggesting a possible explanation for normal glucose uptake during exercise in these subjects.”

    From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [99]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [23]23. Zeigerer, A., McBrayer, M. K., and McGraw, T. E. (2004) Mol. Biol. Cell 15, 4406-4415

Cited by

Sorted by citations

Authors
Peck, G. R., Chavez, J. A., Roach, W. G., Budnik, B. A., Lane, W. S., Karlsson, H. K. R., Zierath, J. R., & Lienhard, G. E.
Affiliations
  • Dartmouth College (US)
  • Harvard University (US)
  • Karolinska Institutet (SE)
Corresponding author
Lienhard, Gustav E.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-10
Volume
284
Issue
44
Pages
30016-30023
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1967821760
Cited by
95
References
26
Citations by year
2026: 5 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 8 · 2013: 6 · 2012: 9
FWCI
3.76
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (P30CA023108)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK025336, DK-25336, R56DK042816, R56DK025336, DK42816, R01DK042816)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
TBC1D1, GLUT4 translocation, insulin signaling, Akt phosphorylation, Rab GTPase-activating protein, AS160, muscle glucose uptake, obesity, type 2 diabetes, vastus lateralis, C2C12 myotubes
MeSH terms
Animals, Diabetes Mellitus, Type 2, Insulin, Nuclear Proteins, Phosphorylation, Muscle, Skeletal, GTPase-Activating Proteins, Protein Transport, 3T3-L1 Cells, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 4, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review