Mitogenesis induced by pp60v-src is not accompanied by increased expression of immediate early response genes.
Rat-1 cells infected with a temperature sensitive mutant of RSV (ts LA 29 Rat-1) can be rendered quiescent by serum deprivation at restrictive temperature. Shift to permissive conditions activates the v-src protein tyrosine kinase within 10 minutes and either this stimulus, or serum addition at restrictive temperature, leads to progression of the cell from G0 to G1, S-phase and mitosis. The effects of serum and temperature shift are not synergistic, suggesting that they may operate by convergent mechanisms. However, the characteristic serum-stimulated transient increases in transcripts of three immediate early response genes, c-fos, c-jun and c-myc are absent or much reduced when mitogenesis in ts LA 29 Rat-1 is induced by pp60v-src. Nonetheless, upon activating the pp60v-src protein kinase there is a marked and rapid increase in the ability of ts LA 29 Rat-1 nuclear extracts to retard the gel migration of oligonucleotides containing the AP-1 binding site, indicating that pp60v-src activity leads to an enhanced functioning of Fos and Jun related proteins that may, in turn, affect their transcriptional activation. Furthermore, these findings, and comparison with those of other laboratories, suggest that the mitogenic and transforming activities of pp60v-src have different effects on the transcription of immediate early response genes.
Welham
M J
MJ
Imperial Cancer Research Fund Laboratories, St. Bartholomew's Hospital, Bartholomew Close, London, UK.
Wyke
J A
JA
Lang
A
A
Wyke
A W
AW
D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D008938:Mitosis / Q000187:drug effects*; D009841:Oligonucleotides / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA; D015688:Oncogene Protein pp60(v-src)