CD38 ligation results in activation of the Raf-1/mitogen-activated protein kinase and the CD3-ζ/ζ-associated protein-70 signaling pathways in Jurkat T lymphocytes

Abstract

CD38 ligation with the specific mAb IB4 induced early and late signaling events in Jurkat T cells, as judged by the transient induction of tyrosine phosphorylation of phospholipase C-γ1, c-Cbl, ζ-associated protein (ZAP)-70, She, extracellular signalregu;ated protein kinease-2 (Erk-2) as mitogen-activated protein (MAP) kinase, and increased expression of the activation Ag CD69. In addition, CD 38 ligation induced Ras-dependent evetnts such as Erk-2 mobility shift and increased Erk-2 kinase activity. Further evidence that Erk-2 activation is regulated by CD38 ligation was obtained indirectly with the observed induction of Raf-1, Lck, and Sos-1 mobility shifts, processes that are believed to be dependent, at least in part, on MAP kinase activation, Using a protein tyrosine kinase inhibitor, herbimycin A, or a protein kinase C inhibitor, Ro-31-8220, we found that the anti-CD38-induced Erk-2 activation is both protein tyrosine kinase and protein kinase C dependent. CD38 ligation also resulted in increased CD3-ζ tyrosine phosphorylation and , its association with ZAP-70. CD38 ligation in a Jurkat Lck-deficient mutant, JC-am1, failed to induce substrate tyrosine phosphorylation and activation of Erk-2. These data indicated that in Jurkat T cells, CD38 receptor triggering results in Lck-regulated activation of both Raf-1/MAP kinase and CD3-ζ/ZAP-70/phoSpholipase C-γy1 signaling pathways.