Age-related decline in activation of JNK by TCR- and CD28-mediated signals in murine T-lymphocytes

被引:33
作者
Kirk, CJ
Freilich, AM
Miller, RA
机构
[1] Univ Michigan, Sch Med, Grad Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Coll Literature Sci & Arts, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA
[5] Ann Arbor DVA Med Ctr, Ann Arbor, MI 48109 USA
关键词
D O I
10.1006/cimm.1999.1567
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
c-Jun N-terminal kinase (JNK) is activated when T-lymphocytes are stimulated jointly through the T-cell receptor (TCR) and CD28, and it contributes to T-cell activation and IL-2 production through phosphorylation of transcription factors, including c-Jun, We performed in vitro kinase assays on JNK in CD4(+) T-cells, from young and old mice, activated by antibodies to CD3, CD4, and CD28, and found a similar to 2-fold decline in JNK activity at the peak of activation, but no significant change in the kinetics of stimulation or in the steady-state expression of JNK, We found a similar decline in c-Jun phosphorylation in stimulated CD4(+) T-cells from old mice, suggesting that JNK activation also declined with age in intact cells. Aging does not, however, alter the level of Ras activation by anti-CD3/CD4 +/- anti-CD28 or change the level of Ras protein in CD4(+) cells, suggesting that the JNK defect is due to changes in the regulation of other upstream regulators. Our results suggest that a decline with age in JNK responses may contribute to the decline in proliferation and IL-2 production seen in CD4(+) T-cells from old mice. (C) 1999 Academic Press.
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收藏
页码:75 / 82
页数:8
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