Differential tyrosine phosphorylation of zeta chain dimers in mouse CD4 T lymphocytes: effect of age.
Antibody to the zeta chain of the CD3/TCR signal transduction complex precipitates a series of tyrosine-phosphorylated proteins that can be discriminated by electrophoresis in nonreducing polyacrylamide gels. Stimulation of resting mouse splenic CD4 T cells by cross-linking CD3 to CD4 leads to increases in tyrosine phosphorylation of five such proteins, of which three are likely to be dimeric forms of zeta as judged by behavior on two-dimensional gels. Two other phosphoproteins, of MW 38 and 55 kDa, also coprecipitate with the CD3zeta complex. The level of induced phosphorylation of each of these five stimulus-responsive phosphoproteins declines with donor age, T cells from 18-month-old mice being almost wholly nonresponsive. Resting T cells have only a single major form of tyrosine-phosphorylated zetazeta. Phosphorylation of this rapidly migrating species is not influenced by activation, but is about threefold lower in resting T cells from 12- to 18-month-old mice than in cells from 6-month-old animals. Thus the phosphorylation of the CD3-zeta chain of CD4 T cells from aged mice exhibits abnormalities both in the resting state and within the first 5 min of the activation process.
Garcia
G G
GG
Department of Pathology, University of Michigan School of Medicine, Ann Arbor 48109, USA.
Miller
R A
RA
D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019281:Dimerization; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D014443:Tyrosine