Pathway
Translocation of SLC2A4 (GLUT4) to the plasma membrane
In adipocytes and myocytes insulin signaling causes intracellular vesicles carrying the GLUT4 (SLC2A4) glucose transporter to translocate to the plasma membrane, allowing the cells to take up glucose from the bloodstream (reviewed in Zaid et al. 2008, Leney and Tavare 2009, Bogan and Kandror 2010, Foley et al. 2011, Hoffman and Elmendorf 2011, Kandror and Pilch 2011, Jaldin-Fincati et al. 2017). In myocytes muscle contraction alone can also cause translocation of GLUT4.
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Though the entire pathway leading to GLUT4 translocation has not been elucidated, several steps are known. Insulin activates the kinases AKT1 and AKT2. Muscle contraction activates the kinase AMPK-alpha2 and possibly also AKT. AKT2 and, to a lesser extent, AKT1 phosphorylate the RAB GTPase activators TBC1D1 and TBC1D4, causing them to bind 14-3-3 proteins and lose GTPase activation activity. As a result RAB proteins (probably RAB8A, RAB10, RAB14 and possibly RAB13) accumulate GTP. The connection between RAB:GTP and vesicle translocation is unknown but may involve recruitment and activation of myosins.
Myosins 1C, 2A, 2B, 5A, 5B have all been shown to play a role in translocating GLUT4 vesicles near the periphery of the cell. Following docking at the plasma membrane the vesicles fuse with the plasma membrane in a process that depends on interaction between VAMP2 on the vesicle and SNAP23 and SYNTAXIN-4 at the plasma membrane.
REACT:R-HSA-1445148Reactome
What the reference databases state
Statements
70 statements
70 statements · 1 reference database · Subject: Translocation of SLC2A4 (GLUT4) to the plasma membrane · Sources: Reactome
- ACTB participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- ACTG1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- AKT1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- AKT2 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- ASPSCR1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- C2CD5 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- CALM1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- EXOC1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- EXOC2 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- EXOC3 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- EXOC4 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- EXOC5 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
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- EXOC6 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- EXOC7 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- EXOC8 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- KIF3A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- KIF3B participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- KIFAP3 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- LNPEP participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- MYH9 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- MYO1C participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- MYO5A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- PRKAA2 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- PRKAB1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- PRKAB2 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- PRKAG1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- PRKAG2 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- PRKAG3 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RAB10 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RAB11A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RAB13 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RAB14 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RAB4A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RAB8A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RAC1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RALA participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RALGAPA2 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RALGAPB participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- RHOQ participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- SFN participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- SLC2A4 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- SNAP23 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- STX4 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- STXBP3 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TBC1D1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TBC1D4 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA1A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA1B participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA1C participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA3C participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA3D participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA3E participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA4A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBA8 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBAL3 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB1 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB2A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB2B participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB3 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB4A participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB4B participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB6 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- TUBB8 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- VAMP2 participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- YWHAB participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- YWHAE participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- YWHAG participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- YWHAH participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- YWHAQ participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only
- YWHAZ participates in Translocation of SLC2A4 (GLUT4) to the plasma membraneProteinReactome R-HSA-1445148Inferred only