Dissociation of c-fos induction from protein kinase C-independent mitogenesis in Swiss 3T3 cells.
Bombesin is a potent mitogen for Swiss 3T3 cells and can act synergistically with insulin to stimulate DNA synthesis through protein kinase C-dependent and -independent pathways. One of the earliest nuclear responses of quiescent cells treated with a combination of bombesin and insulin is a dramatic increase in c-fos expression. Here we report that the selective down-regulation of protein kinase C (PKC) caused a 90-97% decrease in the induction of c-fos mRNA and fos protein expression but did not affect the mitogenic response to bombesin and insulin. These observations were confirmed in detailed dose-response and time-course experiments. We conclude that the large induction of c-fos is not an obligatory event for mitogenesis in Swiss 3T3 cells.
Mehmet
H
H
Imperial Cancer Research Fund, Lincoln's Inn Fields, London, UK.
Moore
J P
JP
Sinnett-Smith
J W
JW
Evan
G I
GI
Rozengurt
E
E
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D051379:Mice; D008934:Mitogens; D011493:Protein Kinase C / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011493:Protein Kinase C; D001839:Bombesin