TRANSFERRIN RECEPTOR INDUCES TYROSINE PHOSPHORYLATION IN T-CELLS AND IS PHYSICALLY ASSOCIATED WITH THE TCR XI-CHAIN

In addition to being an iron transporter, the transferrin receptor (Tf R) has been shown to play a role in T cell activation. Stimulation of the TfR with specific Abs results in T cell proliferation, IL-2 secret ion, and protein kinase C activation. In this paper we have analyzed e arly events caused by activation of the TfR. We have found several pro tein substrates to be tyrosine phosphorylated upon TfR stimulation in the human Jurkat T cell line. Interestingly, the TfR induced tyrosine phosphorylation in cell lines expressing TCR but not in TCR-negative m utants. Restoration of the TCR surface expression in these mutants ree stablished the ability of the TfR to induce tyrosine phosphorylation. This result suggests that activation through the TfR is functionally d ependent upon the expression of the TCR. Moreover, the functional rela tionship of the TfR with the TCR complex is also supported by data sho wing that TfR stimulation resulted in the tyrosine phosphorylation of the TCR zeta-chain; conversely, stimulation of the TCR complex resulte d in an increased tyrosine phosphorylation of the TfR. More importantl y, the TfR is shown to associate physically with the TCR zeta-chain as well as with the zeta-binding ZAP70 tyrosine kinase. The TfR/zeta com plex is expressed on the cell surface independent of the expression of the other subunits of the TCR complex. We suggest that the TfR/zeta c omplex is responsible for transducing the TfR-induced signals, and tha t it could serve to amplify signals delivered by Ag binding to the TCR .