Welihinda A A, Kaufman R J
Department of Biological Chemistry and Howard Hughes Medical Research Institute, The University of Michigan Medical Center, Ann Arbor, Michigan 48109-0650, USA.
J Biol Chem. 1996 Jul 26;271(30):18181-7. doi: 10.1074/jbc.271.30.18181.
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.
在真核细胞中，内质网（ER）中未折叠蛋白的积累会导致多种ER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的传感器，它启动了未折叠蛋白信号从内质网到细胞核的传递。我们已经表明，Ire1p受体的细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。细胞质结构域在体内和体外也被证明能形成寡聚体。形成寡聚体的能力主要存在于细胞质结构域的最后130个氨基酸内，该区域对于受体的体外激酶活性是可有可无的。细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。活化的激酶可能将未折叠蛋白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。
