Nuclear phosphotyrosyl-protein with DNA-binding ability in peripheral blood mononuclear cells from systemic lupus...

This study examined the phosphorylation of cytoplasmic and nuclear proteins in peripheral blood mononuclear cells (PBMC) of systemic lupus erythematosus (SLE) patients. The cytoplasmic and nuclear protein kinase activity in PBMC from SLE patients was at least five-fold higher than that of normal healthy subjects. PBMC of SLE patients produced different nuclear endogenous substrates on phosphorylation and also displayed distinct protein kinase activity. Nuclear phosphoproteins, with human PBMC DNA-binding ability, of 38 kD and 70 kD were detected from both SLE patients and normal healthy subjects, while the 40 kD phosphoprotein, with tyrosine as the main phosphorylation residue, was found only in SLE patients. Other nuclear phosphoproteins, and most of the detected cytoplasmic phosphoproteins, were present in higher levels in both normal PBMC with mitogen stimulation, such as PHA, and SLE PBMC. The expression level of the 40 kD nuclear phosphotyrosyl-protein showed a positive correlation with the clinical disease activity of SLE. These results suggest that PBMC from SLE patients had distinct tyrosine protein kinase (TPK) activity and/or a different endogenous substrate of nuclear DNA-binding proteins in tyrosine phosphorylation. The possible significance of tyrosine phosphorylation in PBMC of SLE patients in the pathogenesis, and its clinical meaning, are discussed.