title: Fibronectin-induced VEGF receptor and calcium channel transactivation stimulate GLUT-1 synthesis and trafficking through PPARγ and TC10 in mouse embryonic stem cells.
abstract: Extracellular matrix (ECM) mediates interactions between integrin and growth factor receptor (GFR) or ion channel. Although this crosstalk promotes integration of the downstream signal pathways and then regulates cellular function, the effect of ECM on glucose transporter (GLUT) in stem cells has not been elucidated. Therefore, we examined the effect of fibronectin on GLUT-1 expression, trafficking, and its related signal pathways in mouse embryonic stem cells (mESCs). Fibronectin increased 2-deoxyglucose (DG) uptake and GLUT-1 protein expression that were blocked by transcription or translation inhibitors. Integrin α5β1-bound fibronectin increased 2-DG uptake through cluster formation with vascular endothelial growth factor receptor (VEGFR) 2, and then activated Ras and PI3K/Akt. In another pathway, integrin α5β1 displayed structural and functional interactions with calcium channels, and stimulated 2-DG uptake through calcium influx and PKC activation. Akt and PKC-induced PPARγ phosphorylation enhanced the decreased expression of PPARγ protein, and subsequently increased GLUT-1 protein synthesis and 2-DG uptake. Fibronectin stimulated TC10 activity and cytoskeleton (F-actin) rearrangement, followed by GLUT-1 trafficking. In conclusion, integrin-bound fibronectin stimulates GLUT-1 synthesis through VEGFR2/Ras/PI3K/Akt and calcium channel/Ca(2+)/PKC, which are merged at PPARγ and GLUT-1 trafficking through TC10 and F-actin.
authors: Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute of Veterinary Science, Seoul National University, Seoul, 151-741, South Korea.
authors: Han Na
authors: HN
authors: Suh
authors: Ho Jae
authors: HJ
authors: Han
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D003847:Deoxyglucose; D005353:Fibronectins; D051272:Glucose Transporter Type 1; D039081:Integrin alpha5beta1; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D040262:Receptors, Vascular Endothelial Growth Factor; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; C503260:Rhoq protein, mouse