Wheat germ agglutinin blocks the biological effects of nerve growth factor.

Abstract

The binding of nerve growth factor (NGF) to specific cell surface receptors initiates a variety of effects that lead to the morphological and biochemical differentiation of clonal pheochromocytoma, PC12, cells. The lectin wheat germ agglutinin (WGA) alters the characteristics of NGF-receptor interaction. We have found that treatment of PC12 cells with WGA dramatically and reversibly inhibits the ability of NGF to elicit three distinct biological effects characteristic of NGF action. Two of these events, the rapid ruffling of cell-surface membranes and the stimulation of the phosphorylation of a 250-kD cytoskeletal protein in situ, occur rapidly and are an immediate consequence of receptor occupancy. Both of these effects are blocked by pretreatment of the cells with WGA. WGA was also found to inhibit the NGFstimulated regeneration of neurites that occurs over 1-2 d. Both the WGA inhibition of neurite outgrowth and the phosphorylation of the 250-kD cytoskeletal protein were reversed upon addition of the specific sugar N-acetylglucosamine. These data demonstrate that the WGAinduced changes in the NGF-receptor interaction reflect important alterations in the ability of the receptor to transmit biological signals, resulting in the abrogation of the biological effects of NGF on these cells.

Wheat germ agglutinin inhibits thrombin‐induced rises in cytosolic free calcium and prostacyclin synthesis by human umbilical vein endothelial cells

“…In the present study, we demonstrate that wheat germ ag lu and PG12 production by HUVEC, whereas other lectins with different sugar specificities are ineffective. Because previous studies have demonstrated that WGA does not bind to or inactivate thrombin (Ganguly et al, 19791, it is most likely that WGA either interferes with the binding of thrombin to its binding site or inhibits tional state of the binding site(s), because WGA has been shown to modulate the affinity of nerve growth factor (NGF) receptors for NGF (Buxer et al, 1983) and block the biological effects of NGF (Landrath et al, 1985). The specificity of WGA is relative rather than absolute.…”

“…In addition, WGA may block thrombin-induced rises in [Ca2+li by altering the func-A Histamine HBS . c WGA 4 tional state of the binding site(s), because WGA has been shown to modulate the affinity of nerve growth factor (NGF) receptors for NGF (Buxer et al, 1983) and block the biological effects of NGF (Landrath et al, 1985). The specificity of WGA is relative rather than absolute.…”

Antimitogenic actions of lectins in cultured human fibroblasts

“…In lymphocytes, Con A is a potent mitogen (Powell and Leon, 1970), and in adipocytes, both Con A and WGA mimic the action of insulin by binding directly to insulin receptors (Cuatrecasas and Tell, 1973;Shechter, 1983). In contrast, in PC12 pheochromocytoma cells, WGA inhibits nerve growth factor (NGF)-induced phosphorylation of a 250-kD cytoskeletal protein and NGF-induced neurite outgrowth at concentrations (2.5-10 Fgirnl) which have little effect on NGF binding (Landreth et al, 1985), and in rat pituitary cells, both WGA and Con A (10 pgiml) inhibit gonadotropin releasing hormoneinduced release of leuteinizing hormone (Schvartz and Hazum, 1986). In both PC12 cells and platelets, lectins induce attachment of cell surface proteins to the underlying cytoskeleton (Painter and Ginsberg, 1982;Vale and Shooter, 1982) but the relationship between this effect and the biological actions of lectins has not been established.…”

Transmembrane Signals and Protooncogene Induction Evoked by Carcinogenic Metals and Prevented by Zinc

“…Cell-surface receptors for hormones usually contain oligosaccharides, which are attached to asparagine residues in the external domain of the receptor (67)(68)(69). Cell-agglutinating, sugar-specific lectins bind the N-linked oligosaccharides of hormone receptors (67,(70)(71)(72)(73). Chen (39) screened a variety of lectins for an effect on Cd2+-evoked Ca2+ mobilization.…”