Two regions of GLUT 2 glucose transporter protein are responsible for its distinctive affinity for glucose.
The glucose transporter in the hepatocyte and pancreatic beta-cell (GLUT 2) has a lower affinity for glucose than other members of the glucose transporter family. To investigate the molecular mechanism for the distinctive affinity of GLUT 2 for glucose, we expressed chimeric GLUT 2 and GLUT 4 proteins in Xenopus oocytes and measured 3-O-methyl-D-glucose transport. In the oocyte system, GLUT 2 had a Km of 31.8 +/- 2.8 mM for 3-O-methyl-D-glucose, whereas GLUT 4 had a Km of 7.2 +/- 2.4 mM under equilibrium exchange conditions. GLUT 4/GLUT 2 chimera that contained the intracellular loop and transmembrane domains 7-12 of GLUT 2 (amino acids 239-497) had a Km similar to that of wild-type GLUT 2. A GLUT 4/GLUT 2 chimera in which the COOH-terminal 30 amino acids of GLUT 4 were replaced with the corresponding region of GLUT 2 had a 2-fold higher Km than GLUT 4, but still had a much lower Km than GLUT 2. These results indicate that both transmembrane domains 7-12 and the COOH-terminus of the protein are responsible for the distinctive glucose affinity of GLUT 2.
Buchs
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Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Wu
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Morita
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Whitesell
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Powers
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D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D009124:Muscle Proteins; D009865:Oocytes / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014982:Xenopus laevis
D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; D005947:Glucose