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Impairment in a negative regulatory system for TCR signaling in CD4 + T cells from old mice
Author(s) -
Inomata Mitsushi,
Shimada Yukiko,
Hayashi Masami,
Shimizu Jun,
Ohno-Iwashita Yoshiko
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.05.063
Subject(s) - lipid raft , regulator , microbiology and biotechnology , kinase , phosphorylation , biology , t cell receptor , signal transduction , src family kinase , negative regulator , proto oncogene tyrosine protein kinase src , chemistry , endocrinology , t cell , immunology , biochemistry , gene , immune system
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.