Stress stimuli-induced lymphocyte activation.
Oxidants, heavy metals, and heat shock, collectively known as stress stimuli, induce the synthesis of a variety of proteins, termed stress proteins, and enhance glucose uptake. In this study, we have demonstrated that stress stimuli enhance protein tyrosine phosphorylation (PTyr-P), modulate protein tyrosine phosphatase (PTPase) activity, activate the src family protein tyrosine kinase (PTK), p56lck, and enhance glucose uptake in human peripheral blood mononuclear cells. The heavy metal Hg2+ and heat shock stimulated PTPase activity at an optimal dose, whereas the oxidant phenylarsine oxide (PAO) was only marginally stimulatory. Treatment of lymphocytes with stress stimuli at a dose which activated PTPase did not produce discernable PTyr-P using Western blotting techniques. PTyr-P was only seen at doses of stress stimuli which were associated with an inhibition of PTPase activity. We could demonstrate a correlation between the dose of stress stimuli effective in increasing PTPase activity and p56lck activation using heat shock and Hg2+ as stress stimuli. On the other hand, much lower concentrations of PAO were effective in activating PTPase than those effective in eliciting p56lck activation. We could not demonstrate a correlation between an effective dose inducing PTyr-P and glucose uptake. Our data do not permit us to draw a simple correlation between enhancement of PTPase activity, activation of p56lck, induction of PTyr-P, and induction of the biological response. It is possible that both stimulation and inhibition of PTPase could regulate PTyr-P by either activating the src family PTKs or preventing dephosphorylation of target proteins which are involved in the biological response. Our data may also provide the biochemical basis for the previously reported mitogenic effects of Hg2+ on lymphocytes.
Lander
H M
HM
Rogosin Institute, Cornell University Medical College, New York, New York 10021.
Levine
D M
DM
Novogrodsky
A
A
D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008214:Lymphocytes / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D013312:Stress, Physiological / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017027:Protein Tyrosine Phosphatases; D005947:Glucose