ERK5 and ERK2 cooperate to regulate NF-kappa B and cell transformation

We have previously demonstrated an involvement of MEK5 and ERK5 in RafBXB-s timulated focus formation in NIH3T3 cells. We find here that MEK5 and ERK5 cooperate with the RafBXB effecters MEK1/2 and ERK1/2 to induce foci. To fu rther understand MEK5-ERK5-dependent signaling, we examined potential MEK5- ERK5 effecters that might influence focus-forming activity. Consistent with results from our focus-formation assays, constitutively active variants of MEK5 and MEK1 synergize to activate NF-kappaB, and MEK5 and ERK5 are requi red for activation of NP-kappaB by RafBXB. The MEK5-ERK5 pathway is also su fficient to activate both NF-kappaB and p90 ribosomal S6 kinase, Our result s support the hypothesis that NF-kappaB and p90 ribosomal S6 kinase are inv olved in MEK5-ERK5-dependent focus formation and may serve as integration p oints for ERK5 and ERK1/2 signaling.