The unfolded protein response pathway in Saccharomyces cerevisiae - Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation
The unfolded protein response pathway in Saccharomyces cerevisiae - Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation
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DOI：
10.1074/jbc.271.30.18181
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发表时间：
1996-07-26
影响因子：
4.8
通讯作者：
Kaufman, RJ
中科院分区：
文献类型：
--
作者：
Welihinda, AA;Kaufman, RJ
在真核细胞中，内质网（ER）中未折叠蛋白质的积累会导致许多内质网伴侣蛋白的转录诱导。在酿酒酵母中，假定的跨膜受体激酶Ire1p（Ern1p）被认为是内质网中未折叠蛋白质的传感器，它启动未折叠蛋白质信号从内质网到细胞核的传递。我们已经表明，Ire1p受体的胞质结构域确实具有内在的丝氨酸/苏氨酸激酶活性，并且也含有丝氨酸/苏氨酸磷酸化位点。还表明该胞质结构域在体内和体外形成寡聚体。形成寡聚体的能力主要存在于胞质结构域的最后130个氨基酸内，该区域对于受体的体外激酶活性是不必要的。胞质结构域的寡聚化是受体反式磷酸化以及随后激酶功能激活所必需的。激活的激酶可能将未折叠蛋白质信号从内质网传递到细胞核，以激活细胞核中伴侣基因的转录。
In eukaryotic cells, accumulation of unfolded proteins in the endoplasmic reticulum (ER) results in a transcriptional induction of a number of ER chaperone proteins. In Saccharomyces cerevisiae, the putative transmembrane receptor kinase, Ire1p (Ern1p), has been implicated as the sensor of unfolded proteins in the ER that initiates transmittance of the unfolded protein signal from the ER to the nucleus. We have shown that the cytoplasmic domain of Ire1p receptor indeed has intrinsic Ser/Thr kinase activity and contains Ser/Thr phosphorylation sites as well. The cytoplasmic domain is also shown to form oligomers in vivo and in vitro. The ability to form oligomers primarily resides within the last 130 amino acids of the cytoplasmic domain, a region that is dispensable for in vitro kinase activity of the receptor. Oligomerization of the cytoplasmic domains is required for receptor trans-phosphorylation and subsequent activation of the kinase function. The activated kinase may transmit the unfolded protein signal from the ER to the nucleus to activate the transcription of the chaperone genes in the nucleus.