Sefton Lab
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We studied the role of tyrosine protein kinases in the regulation of cell proliferation, malignancy and signal transduction. If it's not obvious, the spinning molecule above is phosphotyrosine. Much of our work was focussed on Lck, which is perhaps the best studied and best understood member of the cytoplasmic, non-receptor tyrosine protein kinases of the Src family.
Lck, a lymphoid cell-specific Src kinase, is known to be required for both the development of T cells in the thymus, and the response of mature T cells to antigen and antigen-presenting cells. We did much of our work with Lck because of its clear importance in the regulation of T cell maturation and activation and in part because Anna Voronova was one of the first to clone the Lck gene while she was a graduate student in the lab.Lck is found at the inner face of the plasma membrane where it interacts with the cytoplasmic tails of CD4 in T helper cells and CD8 in cytotoxic T cells. The initial intracellular biochemical event in T cell activation appears to be the phosphorylation of the T cell receptor CD3 and zeta chains by Lck.
We studied the regulation of the activity of the Lck kinase during T cell activation and its role in T cell leukemogenesis. We were interested in kinases and phosphatases that regulate it, and in regulatory proteins. The simian herpesvirus saimiri encodes a protein called Tip that binds avidly to Lck and activates it dramatically. We studied how this occurs and what role this activation plays in the induction of fatal T cell leukemia by this virus.
Our lab faced the courtyard between the two original buildings at the Salk Institute.
We could be found to the right at the far end of the courtyard in this picture.
