Tyrosine-specific protein phosphorylation in response to anti-CD3 antibody is diminished in old mice.
Antiphosphotyrosine immunoblots were used to characterize phosphotyrosine-containing proteins (PY-PPNs) in anti-CD3 stimulated murine T lymphocytes. Activation led to increased phosphorylation of three PY-PPNs (MWs of 120, 80, and 40 kD) within 2 minutes, and maximal phosphoprotein levels were sustained for at least 30 min. There was a progressive decline with age in the responses of these three PY-PPNs to anti-CD3 stimulation, and some 20-23-month-old mice were virtually nonresponsive. A second group of PY-PPNs was present in unstimulated cells and not affected by anti-CD3 treatment or by age. Responses to Con A and to an antibody to the T-cell receptor were also found to be lower in old mice. Our data show that the pattern of tyrosine-specific phosphorylation in normal murine T cells is similar but not identical to patterns previously defined in murine tumor T-cell lines, and that T cells in old mice have defects in tyrosine-specific phosphorylation that could contribute to their diminished responsiveness to mitogenic stimuli.
Shi
J
J
Institute of Gerontology, University of Michigan, Ann Arbor 48109.
Miller
R A
RA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000906:Antibodies; D001345:Autoradiography; D015153:Blotting, Western; D003208:Concanavalin A / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008970:Molecular Weight; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D000906:Antibodies; D003208:Concanavalin A; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases