Welham M J, Wyke J A, Lang A, Wyke A W
Imperial Cancer Research Fund Laboratories, St. Bartholomew's Hospital, Bartholomew Close, London, UK.
Oncogene. 1990 Feb;5(2):161-9.
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.
感染劳斯肉瘤病毒温度敏感突变体(ts LA 29 Rat-1)的大鼠1型细胞,在限制温度下通过血清剥夺可进入静止状态。转移至允许条件下,10分钟内即可激活v-src蛋白酪氨酸激酶,这种刺激或者在限制温度下添加血清,都会使细胞从G0期进入G1期、S期并进行有丝分裂。血清和温度变化的影响并非协同作用,这表明它们可能通过趋同机制发挥作用。然而,当ts LA 29 Rat-1中的有丝分裂由pp60v-src诱导时,血清刺激下三个即时早期反应基因c-fos、c-jun和c-myc转录本典型的短暂增加并不存在或大幅减少。尽管如此,激活pp60v-src蛋白激酶后,ts LA 29 Rat-1核提取物阻滞含有AP-1结合位点的寡核苷酸凝胶迁移的能力会显著快速增加,这表明pp60v-src活性导致Fos和Jun相关蛋白功能增强,进而可能影响它们的转录激活。此外,这些发现以及与其他实验室结果的比较表明,pp60v-src的促有丝分裂和转化活性对即时早期反应基因的转录有不同影响。