Activation signal transduction by proline-rich tyrosine kinase 2 (PYK2) in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

To explore the role of proline-rich tyrosine kinase 2 (PYK2) in systemic lupus erythematosus (SLE), we studied the expression, activation, and function of PYK2 in peripheral blood mononuclear cells (PBMC) from 36 SLE patients. As controls, samples from 19 patients with rheumatoid arthritis and 15 healthy individuals were studied simultaneously. We found a significant increase of both the total PYK2 protein and its activated/phosphorylated form in PBMCs from patients with SLE, particularly those with the complication of nephritis (WHO class IV). There is a clear correlation between the activation of PYK2 and the level of serum complements. In active SLE patients, activation of PYK2 in PBMCs accompanies the increased cell proliferation and the induced expression of co-stimulatory molecules CD40L and CTLA4. These results indicate that phosphorylated PYK2 may induce the expression of CD40L and CTLA4, and subsequently the cell proliferation. PYK2 signaling enhances the autoreactive lymphocyte activation and plays an important role in the pathogenesis of SLE.