The small G-proteins Rap 1 as potential targets of vasoactive intestinal peptide effects in the human colonic cancer cells HT29

We recently reported that the vasoactive intestinal peptide (VIP) potently inhibited proliferation and induced in parallel a strong cAMP rise, in the human colonic cancer cell line HT29. In this study, we investigated whether Rap 1 proteins could be potential targets of VIP effects in HT29 cells. Th ese Pas-related proteins in which activity was demonstrated to be regulated by PKA phosphorylation, are considered as potential modulators of the Pas / Raf / MAP kinases cascade that governs cell growth control. Our data reve aled that the Rap la isoform is highly expressed in HT29 cells and mainly l ocalized in a late endosomal compartment. In these cells, VIP induces Rap 1 phosphorylation and a yet unidentified modification that leads to their ac idification. This latter Rap 1 acidification seems to be, at least partiall y, cAMP-dependent. It is concluded that in HT29 cells, Rap 1 proteins may b e part of a VIP-induced signaling cascade.