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J Biol Chem, Vol. 274, Issue 29, 20633-20642, July 16, 1999

The CD3-gamma delta epsilon Transducing Module Mediates CD38-induced Protein-tyrosine Kinase and Mitogen-activated Protein Kinase Activation in Jurkat T Cells

Mercedes ZubiaurDagger , María GuiradoDagger , Cox Terhorstparallel , Fabio Malavasi**, and Jaime SanchoDagger

From the Dagger  Instituto de Parasitología y Biomedicina, Consejo Superior de Investigaciones Científicas, 18001 Granada, Spain, the parallel  Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, and the ** Institute of Biology and Genetics, University of Ancona Medical School, 60131 Ancona, Italy

We have examined the ability of the CD3-gamma delta epsilon and CD3-zeta signaling modules of the T cell receptor (TCR) to couple CD38 to intracellular signaling pathways. The results demonstrated that in TCR+ T cells that express the whole set of CD3 subunits CD38 ligation led to complete tyrosine phosphorylation of both CD3-zeta and CD3-epsilon polypeptide chains. In contrast, 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-tyrosine 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 phosphorylation of the chimeric receptors, or CD3 subunits, or protein-tyrosine kinase or mitogen-activated protein kinase activation. In summary, these results support a model in which CD38 transduces activating signals inside the cell by means of CD3-epsilon and CD3-zeta tyrosine phosphorylation. Moreover, these data identify the CD3-gamma delta epsilon signaling module as a necessary and sufficient component of the TCR/CD3 complex involved in T cell activation through CD38.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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