Transmodulation of the epidermal-growth-factor receptor in permeabilized 3T3 cells.
Binding of murine epidermal growth factor (EGF) to its high-affinity receptor can be modulated by a variety of structurally unrelated mitogens. The transmodulation, however, is temperature-dependent and has not been observed in isolated membranes. We report here the transmodulation of high-affinity EGF receptors by platelet-derived growth factors (PDGF) and tumour-promoting phorbol esters in 3T3 cells even when they are rendered incapable of fluid-phase endocytosis by treatment with phenylarsine oxide or by permeabilization with lysophosphatidylcholine. The relative affinity of the EGF receptors in the absence of modulating agents is not significantly altered by phenylarsine oxide treatment. Thus the difference in affinity between the two classes of EGF receptors seems to be unrelated to dynamic membrane changes or to differential rates of internalization. In permeabilized cells, non-hydrolysable GTP analogues transmodulate the high-affinity EGF receptor; however, the effects of these analogues are blocked by the protein kinase C inhibitor chlorpromazine. In contrast, transmodulation by PDGF is not blocked by chloropromazine. Thus the high-affinity EGF receptor can be transmodulated by both protein kinase C-dependent or -independent pathways, and the transmodulation processes do not require fluid-phase endocytosis.
Walker
F
F
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Vic., Australia.
Burgess
A W
AW
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability; D002746:Chlorpromazine / Q000494:pharmacology; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009355:Neomycin / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology
D001152:Arsenicals; D009711:Nucleotides; D010982:Platelet-Derived Growth Factor; C029341:oxophenylarsine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D009355:Neomycin; D002746:Chlorpromazine