EGF receptor-mediated signals are differentially modulated by concanavalin A.
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.
Hazan
R
R
Department of Neurobiology, Scripps Research Institute, La Jolla, California 92037.
Krushel
L
L
Crossin
K L
KL
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010766:Phosphorylation; D011233:Precipitin Tests; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D003208:Concanavalin A; C019558:succinylconcanavalin A; D004815:Epidermal Growth Factor; D066246:ErbB Receptors