Impairment in a negative regulatory system for TCR signaling in CD4+ T cells from old mice

Impairment in a negative regulatory system for TCR signaling in CD4+ T cells from old mice
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DOI:
10.1016/j.febslet.2007.05.063
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发表时间:
2007-06-26
期刊:
影响因子:
3.5
通讯作者:
Ohno-Iwashita, Yoshiko
Ohno-Iwashita, Yoshiko
中科院分区:
生物学3区
文献类型:
--
作者:
Inomata, Mitsushi;Shimada, Yukiko;Ohno-Iwashita, Yoshiko

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为了研究脂筏与年龄相关的T细胞功能下降的关系,我们分析了衰老对静息小鼠CD4+ T细胞脂筏成分的影响。我们发现PAG/Cbp有明显的年龄依赖性降低,这与通过将ssk (sks的负调节因子)招募到脂质筏中来调节Sire家族激酶(SFKs)有关。这种减少是T细胞特有的,至少部分归因于其mRNA水平的降低。PAG的减少伴随着向脂质筏募集Csk的显著损伤,以及无活性形式的sfk的减少。这些发现表明老年小鼠CD4+ T细胞在SFK负调控系统中存在缺陷。(c) 2007年欧洲生化学会联合会。Elsevier B.V.版权所有。
To examine the involvement of lipid rafts in an age-associated decline in T cell function, we analyzed the effect of aging on the constituents of lipid rafts in resting mouse CD4+ T cells. We found a pronounced, age-dependent reduction in PAG/Cbp, which is involved in the regulation of Sire family kinases (SFKs) by recruiting Csk (a negative regulator of SFKs) to lipid rafts. This reduction is specific for T cells and is attributed, at least in part, to the reduction in its mRNA level. The reduction of PAG accompanies marked impairment in recruiting Csk to lipid rafts and a concomitant decrease in the inactive forms of SFKs. These findings indicate that old mouse CD4+ T cells have a defect in a negative SFK regulatory system. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.