ArticleMolecular and cellular biology2012
The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Molecular adaptations of adipose tissue to 6 weeks of morning fasting vs. daily breakfast consumption in lean and obese adults.The Journal of physiology · 2018Trial
- TBC1D4-Related Monogenic Diabetes: Molecular Mechanisms, Clinical Recognition, and Therapeutic Implications.Journal of diabetes · 2026Review
- Triglycerides, Glucose Metabolism, and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Glucose-Responsive PAGR1-Regulated Skeletal Muscle Gene Program Controls Systemic Glucose Homeostasis and Hepatic Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unraveling the Mystery of Insulin Resistance: From Principle Mechanistic Insights and Consequences to Therapeutic Interventions.International journal of molecular sciences · 2025Review
- A comprehensiveFrontiers in pharmacology · 2024Review
- Insulin signalling and GLUT4 trafficking in insulin resistance.Biochemical Society transactions · 2023Review
- microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy.Heliyon · 2023Article
- Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism.Frontiers in physiology · 2023Review
- A Cardiac Amino-Terminal GRK2 Peptide Inhibits Maladaptive Adipocyte Hypertrophy and Insulin Resistance During Diet-Induced Obesity.JACC. Basic to translational science · 2022Article
- Article
- GLUT4 On the move.The Biochemical journal · 2022Article
- Magnesium increases insulin-dependent glucose uptake in adipocytes.Frontiers in endocrinology · 2022Article
- WNK1 in Malignant Behaviors: A Potential Target for Cancer?Frontiers in cell and developmental biology · 2022Review
- AKT ISOFORMS-AS160-GLUT4: The defining axis of insulin resistance.Reviews in endocrine & metabolic disorders · 2021Review
- Role of Akt isoforms in neuronal insulin signaling and resistance.Cellular and molecular life sciences : CMLS · 2021Article
- A peptide of the amino-terminus of GRK2 induces hypertrophy and yet elicits cardioprotection after pressure overload.Journal of molecular and cellular cardiology · 2021Article
- Signaling Heterogeneity is Defined by Pathway Architecture and Intercellular Variability in Protein Expression.iScience · 2021Article
- TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes.Scientific reports · 2020Article
- Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes. Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect. In the present study we detected several new functional features of AS160. The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila. This region also contains a nonoverlapping intracellular GLUT4-containing storage vesicle (GSV) cargo-binding site. The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation. Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity. We propose a model wherein AS160 acts as a regulatory switch in the docking and/or fusion of GSVs with the PM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.