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首页> 外文学位 >The regulatory functions of MAPK docking interactions: Jun N-terminal kinase and the c-Jun delta-domain.
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The regulatory functions of MAPK docking interactions: Jun N-terminal kinase and the c-Jun delta-domain.

机译：MAPK对接相互作用的调节功能：Jun N末端激酶和c-Junδ域。

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摘要

Regulation of transcription factor proteins by MAPK signaling cascades is often associated with regulatory phosphorylation reactions. In addition, the ability of inactive MAP kinases to dock their transcription factor targets has been shown to have additional regulatory properties. The transcription factor c-Jun requires phosphorylation by MAPK family member JNK for full activity. The kinase binds at the c-Jun δ-domain and, upon pathway stimulation, phosphorylates Ser63 and Ser73. c-Jun was discovered as v-Jun, the transforming component of the tumor promoting retrovirus, ASV-17. The in-frame deletion of δ-domain is largely responsible for v-Jun's oncogenic properties, but loss of phosphorylation of Ser63/Ser73 is not. This has lead to the widespread belief that transformation is regulated by JNK binding but not catalytic activity. However, the model has never been directly tested.; Through mutational analysis, we were able to identify individual amino acids throughout the δ-domain that are involved in the association with JNK. These mutants enabled us to confirm the requirement of JNK binding for phosphorylation of Ser63/Ser73 and transcriptional activity. In addition, two novel regulatory functions for JNK docking were discovered: repression of c-Jun activity by the association of inactive JNK and the regulation of JNK subcellular localization. Finally, although residues involved in transformation were identified, JNK does not play a direct role in this function. The evidence suggests an unidentified regulatory molecule is responsible.
机译：MAPK信号级联反应对转录因子蛋白的调控通常与调控磷酸化反应有关。另外，已经证明无活性的MAP激酶停靠其转录因子靶标的能力具有额外的调节特性。转录因子c-Jun需要MAPK家族成员JNK的磷酸化才能发挥全部活性。该激酶在c-Junδ结构域结合，并在途径刺激后使Ser63和Ser73磷酸化。 c-Jun被发现为v-Jun，它是促肿瘤逆转录病毒ASV-17的转化成分。 δ结构域的框内缺失在很大程度上负责v-Jun的致癌特性，但不是造成Ser63 / Ser73磷酸化的丧失。这导致人们普遍相信，转化受JNK结合而不是催化活性的调节。但是，该模型从未经过直接测试。通过突变分析，我们能够确定整个δ域中与JNK关联的氨基酸。这些突变体使我们能够确定JNK结合对Ser63 / Ser73磷酸化和转录活性的要求。此外，发现了两个新的JNK对接调节功能：通过非活性JNK的结合抑制c-Jun活性和调节JNK亚细胞定位。最后，尽管确定了参与转化的残基，但JNK在此功能中没有直接作用。证据表明一个未知的调节分子是负责任的。

著录项

  • 作者

    Sprowles, Amy Elizabeth.;

  • 作者单位

    Vanderbilt University.;

  • 授予单位 Vanderbilt University.;
  • 学科 Biology Molecular.; Biology Cell.
  • 学位 Ph.D.
  • 年度 2003
  • 页码 98 p.
  • 总页数 98
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;细胞生物学;
  • 关键词

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