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Cited by 108Cellular transport and secretionMetabolism, Diabetes, and CancerProtein Kinase Regulation and GTPase Signaling

A Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action

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Chen, Xiao-Wei, Leto, Dara, Xiong, Tingting, Yu, Genggeng, Cheng, Alan, Decker, Stuart, Saltiel, Alan R.·2011·Molecular Biology of the Cell
DOI 10.1091/mbc.e10-08-0665PMC PMC3016972
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Abstract

Insulin stimulates glucose transport in muscle and adipose tissue by translocation of glucose transporter 4 (GLUT4) to the plasma membrane. We previously reported that activation of the small GTPase RalA downstream of PI 3-kinase plays a critical role in this process by mobilizing the exocyst complex for GLUT4 vesicle targeting in adipocytes. Here we report the identification and characterization of a Ral GAP complex (RGC) that mediates the activation of RalA downstream of the PI 3-kinase/Akt pathway. The complex is composed of an RGC1 regulatory subunit and an RGC2 catalytic subunit (previously identified as AS250) that directly stimulates the guanosine triphosphate hydrolysis of RalA. Knockdown of RGC proteins leads to increased RalA activity and glucose uptake in adipocytes. Insulin inhibits the GAP complex through Akt2-catalyzed phosphorylation of RGC2 in vitro and in vivo, while activated Akt relieves the inhibitory effect of RGC proteins on RalA activity. The RGC complex thus connects PI 3-kinase/Akt activity to the transport machineries responsible for GLUT4 translocation.

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Cited by

Sorted by citations

Authors
Chen, X.-W., Leto, D., Xiong, T., Yu, G., Cheng, A., Decker, S., & Saltiel, A. R.
Affiliations
  • Life Sciences Institute,
  • University of Michigan (US)
Corresponding author
Saltiel, Alan R.
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2011-01
Volume
22
Issue
1
Pages
141-152
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.e10-08-0665
PMC
PMC3016972
OpenAlex
W2122514972
Cited by
108
References
3
Citations by year
2026: 3 · 2025: 7 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 6 · 2012: 13
FWCI
3.01
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (T32GM007315)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061618, DK076956, DK061618)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
RalA, Akt2 phosphorylation, insulin signaling, GLUT4 translocation, glucose uptake, adipocytes, small GTPase activation, exocyst complex
MeSH terms
Animals, Chlorocebus aethiops, Glucose, Humans, Insulin, Phosphorylation, Blotting, Western, Signal Transduction, Adipocytes, COS Cells, Phosphatidylinositol 3-Kinases, Catalytic Domain, GTPase-Activating Proteins, ral GTP-Binding Proteins, NIH 3T3 Cells, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 4, Mice, Gene Knockdown Techniques

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