TRIGGERING OF A SUSTAINED CALCIUM RESPONSE THROUGH A P56(LCK)-DEPENDENT PATHWAY BY EXOGENOUS GANGLIOSIDE G(M1) IN HUMAN T-LYMPHOCYTES

Various biologic effects induced by free external gangliosides, including cell-signaling events, have been described in several cell systems, We show in this report that free monosialoganglioside G(M1), following its rapid and saturable binding to the cell membrane of human Jurkat T cells, triggers in a few seconds a sustained elevation of the intracellular free calcium concentration, It also induces in parallel the early tyrosine phosphorylation of numerous proteins, including phospholipase C gamma-1, Parallel experiments performed with asialo-G(M1) or the ceramide part of the molecule do not reproduce these effects, demonstrating the prominent role played by the sialylated part of the ganglioside, A marked conversion of the T cell-specific tyrosine kinase p56(lck) to a slow migrating 60-kDa form is also found following G(M1) addition, It is accompanied in the same time by an increased kinase activity in p56(lck) immunoprecipitates. Finally, the marked calcium response and tyrosine phosphorylations triggered by G(M1) cannot be observed in a p56(lck)-negative T cell variant, Together these results demonstrate that the monosialoganglioside G(M1) can behave as an authentic activation molecule on human T lymphocytes, likely through a p56(lck) tyrosine kinase-dependent pathway.