Lectins activate lymphocyte pyruvate dehydrogenase by a mechanism sensitive to protease inhibitors.
The mitogenic lectins concanavalin A and phytohemagglutinin were found to stimulate pyruvate oxidation in rat mesenteric lymphocytes. Marked cell agglutination accompanied this response. Wheat germ agglutinin, a nonmitogenic lectin, also aggregated lymphocytes but did not cause alteration of pyruvate oxidation. Cell lysates from lectin-treated cells retained their ability to oxidize pyruvate at an elevated rate, indicating that the observed stimulation of pyruvate oxidation was not due to increased transport of labeled pyruvate into the cells. Pyruvate oxidation activity in such lysates was readily sedimented in a mitochondria-enriched cellular fraction, indicating that it reflects mitochondrial pyruvate dehydrogenase. Stimulation of this activity by lectins in intact lymphocytes was inhibited when the cells were incubated under conditions expected to inhibit trypsin-like proteases. Thus, esters of arginine, but not of alanine or tyrosine, blocked stimulation of pyruvate dehydrogenase by the lectins. The data indicate that pyruvate dehydrogenase is activated in lymphocytes treated with mitogenic lectins by a mechanism involving one or more proteolytic reactions. The similarity between the results presented here and those recently reported for insulin action on its target cells [Seals, J. R. & Czech, M. P. (1980) J. Biol. Chem. 255, 6529-6531] suggests that these systems may have similar modes of transmembrane signalling.
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D004789:Enzyme Activation; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology*; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D037102:Lectins; D010835:Phytohemagglutinins; D011480:Protease Inhibitors; D011768:Pyruvate Dehydrogenase Complex; D003208:Concanavalin A