Fig. 10.

Models for ERK-dependent regulation of Cdx2 expression in CRC or TS cells. (A) In CRC cells activation of PKC can lead to the activation of the Ras-regulated Raf–MEK–ERK1/2 pathway, which in turn represses Cdx2 transcription and targets Cdx2 for proteasome-dependent turnover. In addition the activation of the ERK1/2 pathway leads to increased phosphorylation of PKC isoforms at a site associated with their activation, revealing a potential new link between ERK1/2 and the PKCs. In addition to such a feed-forward loop, which could serve to enhance Cdx2 repression still further, the activation of PKC might also repress Cdx2 transcription in an ERK1/2-independent pathway. (B) In TS cells activation of the Ras–Raf–MEK–ERK pathway increases the levels of Cdx2, a process which is required for correct trophoblast cell fate determination. Elf5 levels are also regulated by the Raf–MEK–ERK pathway, at least indirectly, via a co-stimulatory loop between Cdx2 and Elf5 which serves to reinforce the commitment to the trophoblast lineage.