Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor alpha, beta, and gamma chains.

Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor alpha, beta, and gamma chains.
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DOI:
10.1083/jcb.129.1.55
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发表时间:
1995-04
影响因子:
7.8
通讯作者:
DAUTRYVARSAT, A
DAUTRYVARSAT, A
中科院分区:
生物学1区
文献类型:
--
作者:
HEMAR, A;SUBTIL, A;LIEB, M;MORELON, E;HELLIO, R;DAUTRYVARSAT, A

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细胞因子受体家族的成员由在其胞外结构域中具有序列和结构同源性的几个非共价连接的链组成。受体亚家族成员共享至少一种组分:因此白细胞介素(IL)2和IL 15的受体具有共同的β和γ链,而IL 2、4、7和9的受体具有共同的γ链。在人T淋巴细胞系中,通过免疫荧光和共聚焦显微镜分析了IL 2受体在配体结合和内吞作用后的细胞内途径。令人惊讶的是,α、β和γ链在一起被内吞后具有不同的细胞内定位。α链总是在转铁蛋白阳性隔室(早期/再循环内体),在早期和晚期内化时间,但从未检测到rab 7阳性隔室(晚期内体)。另一方面,在后期内化时间,β和γ链被排除在转铁蛋白阳性细胞器之外,并且不与α共定位。此外,在rab 7阳性囊泡中可以发现β。这些差异表明,α链粘附于质膜,而β链和γ链朝向降解途径分选。这三种链在细胞表面上的半衰期也反映了它们在胞吞作用后的不同细胞内命运。β和γ链是非常短寿命的多肽,因为它们在表面上的半衰期仅为约1小时,而α是更稳定的表面蛋白。这首次表明多聚体受体的组分可以沿着内吞途径沿着单独分选。
Members of the cytokine receptor family are composed of several noncovalently linked chains with sequence and structure homologies in their extracellular domain. Receptor subfamily members share at least one component: thus the receptors for interleukin (IL) 2 and IL15 have common beta and gamma chains, while those for IL2, 4, 7, and 9 have a common gamma chain. The intracellular pathway followed by IL2 receptors after ligand binding and endocytosis was analyzed by immunofluorescence and confocal microscopy in a human T lymphocytic cell line. Surprisingly, the alpha, beta, and gamma chains had different intracellular localizations after being endocytosed together. The alpha chain was always in transferrin-positive compartments (early/recycling endosomes), both at early and late internalization times, but was never detected in rab7-positive compartments (late endosomes). On the other hand, at late internalization times, the beta and gamma chains were excluded from transferrin-positive organelles and did not colocalize with alpha. Furthermore, beta could be found in rab7-positive vesicles. These differences suggest that the alpha chain recycles to the plasma membrane, while the beta and gamma chains are sorted towards the degradation pathway. The half-lives of these three chains on the cell surface also reflect their different intracellular fates after endocytosis. The beta and gamma chains are very short-lived polypeptides since their half-life on the surface is only approximately 1 h, whereas alpha is a much more stable surface protein. This shows for the first time that components of a multimeric receptor can be sorted separately along the endocytic pathway.
高亲和力人白细胞介素2受体的p55和P70亚基的共内化。稳定的三元受体复合物的证据。
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发表时间: 1988-11-01
影响因子: 15.3
作者:
FUNG, MR;JU, G;GREENE, WC
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DOI: 10.1126/science.8178155
发表时间: 1994-05-13
期刊: SCIENCE
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发表时间: 1994-11-11
期刊: SCIENCE
影响因子: 56.9
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发表时间: 1985-01-01
影响因子: 11.1
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影响因子: 11.1
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