Figure 1.

Differences in RAF-MEK1/2-ERK1/2 signaling in moDCs and T cells.

(a) LPS-induced TLR4 signaling in moDCs leads among others to the activation of Tpl2, which subsequently activates MEK1/2. MEK1/2 phosphorylates and activates ERK1/2, which negatively regulates the LPS-induced moDC maturation. In contrast, RAF kinases are promoting moDC maturation since their inhibition compromises the LPS-induced surface marker expression and IL-12p70 secretion. The contrary effects of RAF and MEK1/2 kinases suggest that the classical pathway in stimulated moDCs is not linear. The exact mechanism of how RAF kinases are getting activated and through which substrates they may fulfill their function in stimulated moDCs remains to be clarified. (b) In contrast, RAF-MEK1/2-ERK1/2 signaling acts linear upon TCR signaling in T cells, since both inhibition of RAF or MEK1/2 kinases inhibit T cell proliferation.