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Proposed model for JNK and p38 MAPK activation in response to the cytokine TNF-α. TNF-α-induced JNK activation is mediated by TRAF2-dependent recruitment of GCK-GCKR and subsequent activation of the MAP3K MEKK1 (6), whereas TNF-α-induced p38 MAPK activation may be mediated by the RIP1-dependent recruitment of the MAP3K MEKK3 and subsequent activation of MKK3-MKK6. The precise mechanism(s) of RIP1-mediated activation of MEKK3 remains unclear.
