Alternative binding of p56lck 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 stress have revealed that not only does oxidative stress causes random and indiscriminate injury on cells or tissues but it may evoke a cascade of signaling, by which cells may manage themselves to counter the stress. We have previously reported that sulfhydryl oxidation induces tyrosine phosphorylation and activation of a src family protein tyrosine kinase, p56lck, in T lymphocytes (Nakamura et al., 1993, Oncogene 8, 3133-3139). However, the possible difference between receptor-mediated signals and oxidative stress-mediated signals is not clear yet. In this study using cultured peripheral blood T lymphocytes (PBL blasts), we show that upon the sulfhydryl oxidation-induced tyrosine phosphorylation of p56lck, the kinase associates with phosphatidylinositol (PI) 3-kinase p85 subunit via the binding of the C-terminal SH2 domain of p85 to the tyrosine-phosphorylated p56lck. This is in contrast to the association of these two molecules in the case of CD4-p56lck cross-linking or interleukin-2 stimulation, where PI 3-kinase p85 subunit binds to the SH3 or SH3/SH2 domain(s) of p56lck. Thus our results indicate the possibility that T cells may utilize an alternative signaling machinery upon an oxidative stress-induced activation of a src family protein tyrosine kinase, p56lck.
Nakamura
K
K
Department of Biological Responses, Kyoto University, Japan.
Hori
T
T
Yodoi
J
J
D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007163:Immunosorbent Techniques; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases