Co-stimulation-dependent activation of a JNK-kinase in T lymphocytes

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Abstract
Previously we implicated c‐Jun N‐terminal kinase (JNK) as an element that is involved in signal integration during co‐stimulation of T lymphocytes. This pathway has now been traced to an upper level, comprising MAPKK SEK1/MKK4/JNKK1 which, similarly to JNK, must receive input both from the TCR and CD28. A large portion of this input is probably integrated at the level of the Rho‐family protein CDC42 which, here, activates SEK1 and JNK to the level reached by TCR and CD28 stimulation. We have identified another putative SEK/JNK pathway regulator, PKCθ, which in contrast to CDC42, activates SEK and JNK maximally only in conjunction with a calcium signal delivered through calcineurin. Signals originating at the TCR and CD28 may travel down the JNK pathway via PKCθ, calcineurin, CDC42, MEKK1 and SEK1.