Impairment in a negative regulatory system for TCR signaling in CD4+ T cells from old mice |
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Authors: | Inomata Mitsushi Shimada Yukiko Hayashi Masami Shimizu Jun Ohno-Iwashita Yoshiko |
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Affiliation: | Cellular Signaling Group, Research Team for Functional Genomics, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. minomata@tmig.or.jp |
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Abstract: | 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 Src 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. |
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Keywords: | Aging T lymphocytes TCR signaling PAG Csk Lipid rafts |
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