Shamu C E, Walter P
Department of Biochemistry and Biophysics, University of California Medical School, San Francisco, CA 94143-0448, USA.
EMBO J. 1996 Jun 17;15(12):3028-39.
The transmembrane kinase Ire1p is required for activation of the unfolded protein response (UPR), the increase in transcription of genes encoding endoplasmic reticulum (ER) resident proteins that occurs in response to the accumulation of unfolded proteins in the ER. Ire1p spans the ER membrane (or the nuclear membrane with which the ER is continuous), with its kinase domain localized in the cytoplasm or in the nucleus. Consistent with this arrangement, it has been proposed that Ire1p senses the accumulation of unfolded proteins in the ER and transmits the signal across the membrane toward the transcription machinery, possibly by phosphorylating downstream components of the UPR pathway. Molecular genetic and biochemical studies described here suggest that, as in the case of growth factor receptors of higher eukaryotic cells, Ire1p oligomerizes in response to the accumulation of unfolded proteins in the ER and is phosphorylated in trans by other Ire1p molecules as a result of oligomerization. In addition to its kinase domain, a C-terminal tail domain of Ire1p is required for induction of the UPR. The role of the tail is probably to bind other proteins that transmit the unfolded protein signal to the nucleus.
跨膜激酶Ire1p是激活未折叠蛋白反应（UPR）所必需的，UPR是指因内质网（ER）中未折叠蛋白的积累而发生的编码ER驻留蛋白的基因转录增加。Ire1p跨越ER膜（或与ER连续的核膜），其激酶结构域位于细胞质或细胞核中。与这种排列一致的是，有人提出Ire1p感知ER中未折叠蛋白的积累，并可能通过磷酸化UPR途径的下游成分将信号跨膜传递给转录机制。本文所述的分子遗传学和生化研究表明，与高等真核细胞的生长因子受体一样，Ire1p会因ER中未折叠蛋白的积累而发生寡聚化，并由于寡聚化而被其他Ire1p分子反式磷酸化。除了其激酶结构域，Ire1p 的C末端尾巴结构域对于诱导UPR也是必需的。尾巴的作用可能是结合其他将未折叠蛋白信号传递到细胞核的蛋白质。
