Decreased association of p56lck with CD4 may account for lowered tyrosine kinase activity in mitogen-activated human T lymphocytes during aging.
Treatment of T cells from young donors with PHA rapidly induces tyrosine phosphorylation of several intracellular substrates. In contrast, T cells from elderly donors treated in a similar manner showed far fewer tyrosine-phosphorylated proteins. To understand the basis of this age-associated difference in T cells, we examined the in vitro catalytic activity of kinase(s) following activation. We demonstrate both lowered overall in vitro kinase activity as well as a significant decrease in the activity of lymphocyte-specific tyrosine kinase p56lck in activated T cells from the elderly. Our results demonstrate for the first time an altered association of p56lck with coreceptors such as CD4 and CD45 in the elderly. These results suggest that alterations in p56lck tyrosine kinase and its association with CD4 and CD45 may underlie lowered T cell function during aging.
Tinkle
C W
CW
Department of Geriatrics, University of Arkansas School for Medical Sciences, Little Rock 72205, USA.
Lipschitz
D
D
Ponnappan
U
U
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D000081247:CSK Tyrosine-Protein Kinase; D002384:Catalysis; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D015704:CD4 Antigens; D008934:Mitogens; D010835:Phytohemagglutinins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; C000631346:CSK protein, human; D017493:Leukocyte Common Antigens