Convergence of MAP kinase pathways on the ternary complex factor Sap-1a
Convergence of MAP kinase pathways on the ternary complex factor Sap-1a
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DOI：
10.1093/emboj/16.7.1620
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发表时间：
1997-04-01
期刊：
影响因子：
11.4
通讯作者：
Hunter, T
中科院分区：
文献类型：
--
作者：
Janknecht, R;Hunter, T
血清反应元件（SRE）对于c-fos原癌基因转录上调至关重要，由包含血清反应因子和三元复合因子（TCF）的蛋白质复合物组成组成型占据。 MAP 激酶的 ERK 和 JNK 亚类对 TCF Elk-1 和 Sap-1a 的磷酸化会触发 c-fos 转录。我们在此证明，Elk-1 几乎不被 MAP 激酶的第三个亚类 (p38) 激活，很可能是因为关键残基 Ser383 和 Ser389 很难被 p38 MAP 激酶磷酸化。相比之下，TCF Sap-1a 在体外和体内均被 p38 MAP 激酶有效磷酸化，同源残基 Ser381 和 Ser387。这些位点突变为丙氨酸会严重降低 Sap-1a 和 p38 MAP 激酶介导的 c-fos SRE 依赖性转录。因此，Sap-1a 可能是有丝分裂原、应激和细胞凋亡信号引发核反应的重要靶标。然而，从 p38 MAP 激酶到 Sap-1a 或从 Sap-1a 到基础转录机制的信号传导并不发生在所有细胞类型中，也不会发生在除 c-fos SRE 之外的启动子上，这可以确保信号传导的特异性。
The serum response element (SRE), which is pivotal for transcriptional up-regulation of the c-fos protooncogene, is constitutively occupied by a protein complex comprising the serum response factor and a ternary complex factor (TCF). Phosphorylation of the TCFs Elk-1 and Sap-1a by the ERK and JNK subclasses of MAP kinases triggers c-fos transcription. We demonstrate here that Elk-1 is barely activated by a third subclass of MAP kinases (p38), most likely because the critical residues Ser383 and Ser389 are poorly phosphorylated by p38 MAP kinase. In contrast, the TCF Sap-1a is efficiently phosphorylated by p38 MAP kinase in vitro and in vivo an the homologous residues Ser381 and Ser387. Mutation of these sites to alanine severely reduces c-fos SRE-dependent transcription mediated by Sap-1a and p38 MAP kinase. Thus, Sap-1a may be an important target for mitogens, stress and apoptotic signals to elicit a nuclear response. However, signaling from p38 MAP kinase to Sap-1a or from Sap-1a to the basal transcription machinery does not occur in all cell types nor at promoters other than the c-fos SRE, which may ensure the specificity of signaling.