The CD3-gamma delta epsilon transducing module mediates CD38-induced protein-tyrosine kinase and mitogen-activated protein kinase activation in Jurkat T cells

We have examined the ability of the CD3-gamma delta epsilon and CDS-zeta si gnaling modules of the T cell receptor (TCR) to couple CD38 to intracellula r signaling pathways. The results demonstrated that in TCR+ T cells that ex press the whole set of CD3 subunits CD38 ligation led to complete tyrosine phosphorylation of both CD3-zeta and CD3-epsilon polypeptide chains. In con trast, in TCR+ cells with a defective CD3-zeta association CD38 engagement caused tyrosine phosphorylation of CD3-epsilon but not of CD3-zeta. Despite these differences, in both cell types CD38 ligation resulted in protein-ty rosine kinase and mitogen-activated protein kinase activation. However, in cells expressing chimerical CD25-zeta or CD25-epsilon receptors or in a TCR -beta(-) Jurkat T cell line, CD38 ligation did not result in tyrosine phosp horylation of the chimeric receptors, or CD3 subunits, or protein-tyrosine kinase or mitogen-activated protein kinase activation. In summary, these re sults support a model in which CD38 transduces activating signals inside th e cell by means of CD3-epsilon and CD3-zeta tyrosine phosphorylation. Moreo ver, these data identify the CD3-gamma delta epsilon signaling module as a necessary and sufficient component of the TCR/CD3 complex involved in T cel l activation through CD38.