LIGATION OF THE T-CELL RECEPTOR COMPLEX RESULTS IN ACTIVATION OF THE RAS RAF-1/MEK/MAPK CASCADE IN HUMAN T-LYMPHOCYTES/

Stimulation of T cells with antibodies directed towards the T cell rec eptor complex results in the activation of mitogen-associated protein kinase (MAPK). Two pathways have been described in other cell types th at can lead to MAPK activation. One of these pathways involves the act ivation of Ras, leading to the activation of Raf-1, and the subsequent activation of MEK (MAPK or ERK kinase). The contribution of this path way in T cells for anti-CD3 or phorbol myristate acetate (PMA)-mediate d MAPK activation was examined. We detected the kinase activities of R af-1 and MEK towards their substrates (MEK for Raf-1 and MAPK for MEK) in this pathway leading to the activation of MAPK. Stimulation of the T cells with either anti-CD3 antibody or PMA resulted in a rapid acti vation of both Ras and Raf-1. MEK activity towards kinase-active or -i nactive recombinant MAPK also increased upon stimulation. In addition, both MAPK and p90(rsk) were activated in these cells. We suggest that activation of MAPK and the subsequent activation of ribosomal S6 kina se (p90(rsk)) occurs by the Ras/Raf-1/MEK cascade in T lymphocytes sti mulated by ligation of the T cell receptor complex.