Impairment in a negative regulatory system for TCR signaling in CD4+ T cells from old mice.
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.
Inomata
Mitsushi
M
Cellular Signaling Group, Research Team for Functional Genomics, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. minomata@tmig.or.jp
Shimada
Yukiko
Y
Hayashi
Masami
M
Shimizu
Jun
J
Ohno-Iwashita
Yoshiko
Y
D000375:Aging / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D000081247:CSK Tyrosine-Protein Kinase; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014018:Tissue Distribution; D019061:src-Family Kinases / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C408344:Pag protein, mouse; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases