In vivo dissection of lymphocyte signaling pathways

Abstract

Attempts to dissect signaling pathways leading from the T cell antigen receptor to the cell interior rely primarily on careful biochemical analysis of changes in cellular metabolism provoked by ligand. An alternative approach tests hypotheses regarding the mechanism of T cell activation by altering the representation of putative signaling molecules in otherwise normal lymphocytes using gene manipulation techniques. Rigorous implementation of this strategy has defined crucial roles for two protein tyrosine kinases, p56lck and p59fyn, in T cell signaling pathways. Working from this strong foundation, a molecular description of the T cell activation sequence may now be achievable.