Signal transduction through epidermal growth factor receptor is altered in HeLa monolayer cells during mitosis.
Epidermal growth factor (EGF)-induced signalling was studied separately in the mitosis and G2-phases of HeLa monolayer cells presynchronized (1) by amethopterin inhibition and thymidine release or (2) by nocodazole. For comparison, cells were treated with the phorbol ester phorbol 12-myristate 13-acetate (PMA). In contrast with the observed responses effected by PMA, which seem to be independent of cell cycle and synchronization conditions, those induced by EGF are greatly influenced by both criteria. Synchronization with nocodazole abolished the EGF-induced stimulation of phosphoinositide hydrolysis in G2 as well as in mitotic cells although tyrosine phosphorylation of the EGF receptor and phospholipase Cgamma1 could be shown to occur, especially in G2 cells. Synchronization with amethopterin/thymidine showed that, in contrast with G2 cells, mitotic cells were not able to react to EGF with an increase in phosphoinositide hydrolysis although a certain degree of EGF receptor dimerization and autophosphorylation as well as tyrosine phosphorylation of phospholipase Cgamma1 could still be shown to occur in mitosis. The results seem to indicate that the EGF pathway leading to a stimulation of phosphoinositide hydrolysis is attenuated at different levels and requires a cytoskeletal condition that is not present either after treatment (24 h) with nocodazole or during normal mitosis of a monolayer cell.
Klein
S
S
Department of Pathochemistry 0210, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Federal Republic of Germany.
Kaszkin
M
M
Barth
H
H
Kinzel
V
V
D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D015739:Nocodazole / Q000494:pharmacology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000970:Antineoplastic Agents; D002273:Carcinogens; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate; D015739:Nocodazole