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ζ链在T细胞抗原受体表达中的作用:基因重组研究

Role of the zeta chain in the expression of the T cell antigen receptor: genetic reconstitution studies.

作者信息

Weissman A M, Frank S J, Orloff D G, Merćep M, Ashwell J D, Klausner R D

机构信息

Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD.

出版信息

EMBO J. 1989 Dec 1;8(12):3651-6. doi: 10.1002/j.1460-2075.1989.tb08539.x.

Abstract

The zeta (zeta) chain plays a central role in T cell antigen receptor assembly and signal transduction. From previous work in murine T cell hybridomas we have inferred that the zeta subunit is limiting in receptor assembly. Partial receptors made in excess of zeta are assembled in the endoplasmic reticulum, transported through the Golgi, but then rapidly and efficiently degraded in lysosomes. zeta would therefore seem to play a unique role in targeting receptors from the Golgi to the cell surface. To determine directly whether zeta limits receptor assembly we have reconstituted a zeta-deficient T cell line by transfection of the murine zeta cDNA. Transfection results in restoration of expression of surface T cell receptor. In addition, increasing zeta expression results in a commensurate increase in the survival of previously excess subunits. This is reflected in an increased surface expression of complete receptors. Finally, transfection of the zeta cDNA fails to produce detectable zeta-eta heterodimers. The implications of these findings with regard to receptor assembly, and the relationship between zeta and eta, are discussed.

摘要

ζ链在T细胞抗原受体组装和信号转导中起核心作用。根据之前在小鼠T细胞杂交瘤中的研究工作,我们推断ζ亚基在受体组装中起限制作用。超过ζ量产生的部分受体在内质网中组装,通过高尔基体运输,但随后在溶酶体中迅速且有效地降解。因此,ζ似乎在将受体从高尔基体靶向细胞表面中发挥独特作用。为了直接确定ζ是否限制受体组装,我们通过转染小鼠ζ cDNA重建了一个ζ缺陷的T细胞系。转染导致表面T细胞受体表达的恢复。此外,增加ζ表达会使先前过量亚基的存活率相应增加。这反映在完整受体的表面表达增加上。最后,转染ζ cDNA未能产生可检测到的ζ-η异二聚体。讨论了这些发现对受体组装的意义以及ζ与η之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea8/402047/d64373925aec/emboj00136-0112-a.jpg

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