EGF receptor‐mediated signals are differentially modulated by concanavalin A

Abstract

NIH 3T3 cells expressing high levels of the human epidermal growth factor (EGF) receptor were used to examine the effects of the lectin concanavalin A (Con A) on EGF-mediated signaling events. Proliferation of NIH 3T3 cells expressing high levels of the human EGF receptor was inhibited in a dose-dependent manner by Con A. At the same time, Con A also inhibited both dimerization and tyrosine phosphorylation of the EGF receptor. Tyrosine phosphorylation of the enzyme phospholipase C-gamma, a substrate of the phosphorylated EGF receptor kinase, was also inhibited. In contrast, EGF-stimulated changes in pH, calcium, and levels of inositol phosphates were unaffected by the presence of Con A. These results indicate that certain signals (changes in the levels of intracellular calcium, pH, and inositol phosphates) mediated by EGF binding to its receptor still occur when receptor dimerization and phosphorylation are dramatically decreased, suggesting that multiple independent signals are transmitted by the binding of EGF to its receptor.

Asialoglycoprotein Receptor Promotes Cancer Metastasis by Activating the EGFR–ERK Pathway

“…The activation of the EGFR-ERK pathway mediates cell proliferation in a biphasic, dose-dependent manner (42,43). However, O-charoenrat and colleagues showed that MMP-9 induction in head and neck squamous carcinoma cells increased in an EGF concentration-dependent manner (44).…”

Inhibition of AT1 Receptor Internalization by Concanavalin A Blocks Angiotensin II-induced ERK Activation in Vascular Smooth Muscle Cells

“…ConA polyclonally activates T cells (47). On the other hand, ConA inhibits internalization of EGF receptor and the receptor-mediated mitogenic effects without affecting EGF binding and EGF-stimulated changes in pH, calcium, and levels of inositol phosphates in NIH 3T3 cells (48,49 (36 -39). These sites bind a variety of downstream signaling proteins that contain Src homology 2 domains, including Shc (40) and phospholipase C␥ (41), thus leading to ERK activation.…”

Core Fucosylation Regulates Epidermal Growth Factor Receptor-mediated Intracellular Signaling

“…The binding of these ligands to the extracellular domain of EGFR induces activation of its intrinsic tyrosine kinase activity, leading to the receptor autophosphorylation and the phosphorylation of tyrosine residues in various cellular substrates, many of which serve as intracellular signal molecules (17)(18)(19). The extracellular domain of EGFR contains 12 potential N-glycosylation sites (20), and the remodeling of N-glycans on EGFR can modulate EGFR-mediating functions (21)(22)(23)(24)(25)(26). It has been reported that the binding of EGF to EGFR was significantly reduced by treatment with some N-glycosylation inhibitors (21).…”

“…It has been reported that the binding of EGF to EGFR was significantly reduced by treatment with some N-glycosylation inhibitors (21). In addition, EGF binding as well as its tyrosine kinase activity was reduced by addition of certain lectins (22)(23)(24), indicating that N-glycans are required for ligand binding. On the other hand, the overexpression of N-acetylglucosaminyltransferase III (GnT-III), a pivotal glycosyltransferase that plays a major role in the biosynthesis of hybrid and complex types of N-linked oligosaccharides (27), significantly reduces the ability of EGF to bind to its receptor, EGFR autophosphorylation, and subsequently blocks EGFR-mediated ERK phosphorylation in U373 MG glioma cells (25) or PC12 cells (26).…”