Cross-linking of EphB6 resulting in signal transduction and apoptosis in Jurkat cells

Eph kinases are the largest family of receptor tyrosine kinases (RTK), and their ligands are cell surface molecules. The known functions of Eph kinase s are mainly pattern formation in the CNS. Although several Eph kinases are expressed at high levels in hemopoietic cells and in the thymus, we have n o knowledge of the functions of any Eph kinase in the immune system. In thi s study, we have demonstrated that an Eph kinase, EphB6, was expressed at h igh levels in Jurkat leukemic T cells. Co-cross-linking of EphB6 and CD3 le d to an altered profile of lymphokine secretion along with proliferation in hibition of Jurkat cells. The cells subsequently underwent Fas-mediated apo ptosis. Although EphB6 has no intrinsic kinase activity, its cross-linking triggered general protein tyrosine phosphorylation in Jurkat cells. EphB6 w as found to associate with a number of molecules in the signaling pathways, notably Cbl. EphB6 cross-linking resulted in Cbl dephosphorylation and dis sociation from Src homology 2 domain-containing tyrosine phosphatase-1 (SHP -1). Our results show that EphB6 has important functions in T cells, and it can transduce signals into the cells via proteins it associates with.