Modulation of the synthesis and glycosylation of the glucose transporter protein by transforming growth factor-beta 1 in Swiss 3T3 fibroblasts.
Transforming growth factor-beta 1 (TGF-beta 1) stimulated growth and glucose uptake in Swiss mouse fibroblasts. DNA synthesis was increased 2-3-fold after 48 h incubation of growing 3T3 cells with TGF-beta 1 in calf serum-containing medium. Glucose transport activity in the cells was increased within 3 h after addition of TGF-beta 1 and this stimulation continued during incubation for 48 h. TGF-beta 1 also increased the levels of a brain type-glucose transporter (GLUT1) mRNA and the GLUT1 protein (55 kDa) in the membranes, consistent with the increase in glucose uptake. Furthermore, a longer exposure of TGF-beta 1 for 24-48 h induced a marked increase in the 65 kDa GLUT1 in 3T3 cell membranes. Other growth factors such as epidermal growth factor, fibroblast growth factor, transforming growth factor-alpha, and insulin did not elevate glucose uptake and the levels of 55 and 65 kDa GLUT1 proteins. Adding tunicamycin or deoxymannojirimycin to the TGF-beta 1-treated and untreated cells caused these 55 and 65 kDa glucose transporters to migrate as one band at 40-43 kDa. In addition, treating membrane proteins with glycopeptidase F, which removes N-linked oligosaccharides, also generated a glucose transporter of 40 kDa, suggesting that the 55 and 65 kDa GLUT1 proteins have a similar or identical core polypeptide but with different N-linked oligosaccharides. These results indicate that TGF-beta 1 modulates the synthesis of GLUT1 protein as well as its glycosylation in Swiss 3T3 cells, and that these changes may contribute to the control of cell proliferation by TGF-beta 1.
Masumi
A
A
Department of Chemistry, National Institute of Health, Tokyo, Japan.
Akamatsu
Y
Y
Kitagawa
T
T
D016475:3T3 Cells / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication; D003847:Deoxyglucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051272:Glucose Transporter Type 1; D006031:Glycosylation / Q000187:drug effects; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D013268:Stimulation, Chemical; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; D016212:Transforming Growth Factor beta; D014415:Tunicamycin; D003847:Deoxyglucose