ALTERNATIVE BINDING OF P56(LCK) AND PHOSPHATIDYLINOSITOL 3-KINASE IN T-CELLS BY SULFHYDRYL OXIDATION - IMPLICATION OF ABERRANT SIGNALING DUE TO OXIDATIVE STRESS IN T-LYMPHOCYTES

Recent studies of the physiological effects induced by oxidative stres s have revealed that not only does oxidative stress causes random and indiscriminate injury on cells or tissues but it may evoke a cascade o f signaling, by which cells may manage themselves to counter the stres s. We have previously reported that sulfhydryl oxidation induces tyros ine phosphorylation and activation of a src family protein tyrosine ki nase, p56(lck), in T lymphocytes (Nakamura et al., 1993, Oncogene 8, 3 133-3139). However, the possible difference between receptor-mediated signals and oxidative stress-mediated signals is not clear yet. In thi s study using cultured peripheral blood T lymphocytes (PBL blasts), we show that upon the sulfhydryl oxidation-induced tyrosine phosphorylat ion of p56(lck), the kinase associates with phosphatidylinositol (PI) 3-kinase p85 subunit via the binding of the C-terminal SH2 domain of p 85 to the tyrosine-phosphorylated p56(lck). This is in contrast to the association of these two molecules in the case of CD4-p56(lck) cross- linking or interleukin-2 stimulation, where PI 3-kinase p85 subunit bi nds to the SH3 or SH3/SH2 domain(s) of p56(lck). Thus our results indi cate the possibility that T cells may utilize an alternative signaling machinery upon an oxidative stress-induced activation of a src family protein tyrosine kinase, p56(lck). Copyright (C) 1996 Elsevier Scienc e Ltd