需要一种具有cdc2+/CDC28相关的激酶活性的跨膜蛋白来从ER向细胞核发送信号
1Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
Cell
|August 27, 1993
概括
酵母突变发现了ERN1基因.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞拥有从内细胞网 (ER) 到细胞核的信号通路.
- 这条通路对ER中未折叠的蛋白质的积累作出反应,这种情况被称为ER压力.
- 这种应激反应对于细胞生存至关重要.
研究的目的:
- 调查酵母菌中ER-to-nucleus应激反应途径背后的分子机制.
- 为了识别和表征参与这种途径的基因,特别关注ERN1基因.
- 阐明ERN1基因产物Ern1p在感知和转换ER压力信号中的功能.
主要方法:
- 在ER应激反应通路中存在缺陷的酵母突变的遗传分析.
- 基因映射以确定ERN1的位置.
- 对ERN1基因及其编码的蛋白质Ern1p的分子表征.
- 生物化学测试以确定Ern1p.p.的蛋白激酶活性.
主要成果:
- 确定了几种在ER应激反应通路中存在缺陷的酵母突变.
- 这些突变物与ERN1基因进行了映射.
- ERN1编码了一个具有细胞质蛋白激酶域的跨膜蛋白 (Ern1p).
- 建议Ern1p是ER事件的近距离传感器.
结论:
- ERN1基因在保护酵母细胞免受致命的ER压力方面发挥着至关重要的作用.
- Ern1p作为一个跨膜传感器,通过ER膜传输信号.
- 激活Ern1p导致转录因子的激活,增加保护性ER蛋白的表达,如BiP.
相关概念视频
01:24Intracellular Signaling Cascades
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:26Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...