Schönthal A, Alberts A S, Frost J A, Feramisco J R
Cancer Center, University of California, San Diego, La Jolla 92093-0636.
New Biol. 1991 Oct;3(10):977-86.
Phosphorylation events are major regulatory mechanisms of signal transduction pathways that control cell growth and differentiation. The potential involvement of serine/threonine-specific phosphoprotein phosphatases in pathways that regulate gene expression was analyzed. By use of okadaic acid, an inhibitor of protein phosphatases 1 (PP-1) and 2A (PP-2A), we present evidence that expression of distinct members of the jun family of genes, c-jun, junB, and junD, are regulated differentially by serine/threonine-specific phosphoprotein phosphatases. Treatment of cells with okadaic acid induces the expression of junB, and to a lesser extent c-jun, but has only a marginal effect on junD expression. This induction involves transcriptional as well as post-transcriptional mechanisms. An analysis of defined elements in different promoters suggests that serine/threonine phosphoprotein phosphatases are involved in the regulation of the c-jun and the collagenase 12-O-tetradecanoyl phorbol-13-acetate (TPA) response element (TRE) as well as the c-fos serum response element (SRE). Since inhibition of PP-1 and PP-2A leads to increased proto-oncogene expression, our results further support the view that certain protein phosphatases might act as negative regulators of growth.
磷酸化事件是控制细胞生长和分化的信号转导途径的主要调节机制。分析了丝氨酸/苏氨酸特异性磷蛋白磷酸酶在调节基因表达途径中的潜在作用。通过使用冈田酸（一种蛋白磷酸酶1（PP - 1）和2A（PP - 2A）的抑制剂），我们提供证据表明，jun基因家族的不同成员c - jun、junB和junD的表达受到丝氨酸/苏氨酸特异性磷蛋白磷酸酶的不同调节。用冈田酸处理细胞可诱导junB的表达，并在较小程度上诱导c - jun的表达，但对junD的表达只有轻微影响。这种诱导涉及转录和转录后机制。对不同启动子中特定元件的分析表明，丝氨酸/苏氨酸磷蛋白磷酸酶参与了c - jun和胶原酶12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）反应元件（TRE）以及c - fos血清反应元件（SRE）的调节。由于抑制PP - 1和PP - 2A会导致原癌基因表达增加，我们的结果进一步支持了某些蛋白磷酸酶可能作为生长负调节因子的观点。
