T cell receptor-associated protein tyrosine kinases: The dynamics of tolerance regulation by phosphorylation and its role in systemic lupus erythematosus

There are different abnormalities that lead to the autoreactive phenotype in T cells from systemic lupus erythematosus (SLE) patients. Proximal signaling, involving the T-cell receptor (TCR) and its associated protein tyrosine kinases (PTKs), is significantly affected in SLE. This ultimately leads to aberrant responses, which include enhanced tyrosine phosphorylation and calcium release, as well as decreased IL-2 secretion. Lck, ZAP70 and Syk, which are PTKs with a major role in proximal signaling, all present abnormal functioning that contributes to an altered T cell response in these patients. A number of other molecules, especially regulatory proteins, are also involved. This review will focus on the PTKs that participate in proximal signaling, with specific emphasis on their relevance in maintaining peripheral tolerance, their abnormalities in SLE and how these contribute to an altered T cell response.