Membrane glycoprotein defects in congenital platelet disorders.

concanavalin A-binding proteins are relatively unaffected by the changes in glucose concentration. At this threshold level of glucose the glucose-regulated proteins of Shui et al. (1977) are not apparent. The reappearance of the 100000-mol.wt. glycoprotein can be correlated with the reappearance of the 95 000-mol.wt. glucosamine-labelled glycoprotein (Fig. 2) and there seems, therefore, good reason to believe that they are linked in some way or involved together in glucose metabolism. The induction of the 100000-mol.wt. glycoprotein is specific for Dglucose and D-mannose at concentrations above 300mg/ litre. L-glucose. deoxy-D-glucose. 5-thio-D-glucose ahd Dgalactose are not inducers, even though deoxy-D-glucose and 5-thio-D-glucose are supposed to enter the cell using the same carrier as D-glucose. Not surprisingly the induction is completely inhibited by cytochalasin B, but is unaffected by cytochalasins A. C or D (Kletzien el al., 1972). It has also been shown that PGI9-G cells grown in low levels of glucose bind only 50% of labelled cytochalasin B compared with the same cells grown in normal levels of glucose, thus providing additional evidence that the glucose carrier protein is much reduced in these cells. Addition of emetine, a specific protein inhibitor, just before glucose is sufficient to completely block the inductive effect, showing that protein synthesis must take place if induction of the 100000-mol.wt. glycoprotein is to occur. Recently it has been demonstrated by radiation-target-size theory that the glucose carrier in human erythrocytes is most likely a protein of mol.wt. 200000 which exists as a dimer of mol.wt.-100000 or a tetramer of mol.wt.-50000 subunits (Jung et al., 1980). Also using a more specific glucose-transport blocking reagent, maltosyl isothiocyanate, Mullins 8c Langdon (1980) confirmed that in the human erythrocyte the glucose carrier is contained in the band 3 proteins (mol.wt. 90000lOO000). It thus seems highly probable that the changes seen in the 100000-rno1.w. and 90000-mol.wt. glycoproteins in malignant transformation are directly related to the glucose uptake by these cells and may well be linked to the glucose-regulated proteins seen by other workers (Shiu et al., 1977; McCormick et al., 1979), but distinct from them, since the former are present in only very small amounts.