The long term goal of this project is to identify and characterize the molecular mechanisms of glucose transport in mammalian tissue. The goal of this proposal is to investigate structure/function relationships of monosaccharide transport in the human erythrocyte.
The specific aims for this application are: (1) to investigate the primary structure of the glucose transporter protein using affinity labeling techniques. New probes will be used in conjunction with peptide mapping to identify the various membrane and cytosolic domains of the transporter. (2) We will also prepare polyclonal antibodies against the transporter and its peptide fragments to be used as structural probes. (3) We will attempt to develop additional affinity techniques in order to improve isolation and purification of this protein. (4) We propose to investigate the modulation of human erythrocyte glucose transport by-ATP and other agents. (5) We will continue to use membrane crosslinking agents to explore the oligomeric structure and environment of the transporter, as well as its transmembrane orientation. (6) Synthesis of additional photoreactive probes of the transporter will also be attempted. These studies may additionally provide a basis for analyzing mechanisms of glucose transport in other systems such as insulin-sensitive tissue, in both normal and disease states.
| Martin, G E; Seamon, K B; Brown, F M et al. (1994) Forskolin specifically inhibits the bacterial galactose-H+ transport protein, GalP. J Biol Chem 269:24870-7 |
| Devaskar, S; Zahm, D S; Holtzclaw, L et al. (1991) Developmental regulation of the distribution of rat brain insulin-insensitive (Glut 1) glucose transporter. Endocrinology 129:1530-40 |
| Wadzinski, B E; Shanahan, M F; Clark, R B et al. (1988) Identification of the glucose transporter in mammalian cell membranes with a 125I-forskolin photoaffinity label. Biochem J 255:983-90 |
