1. The small G-proteins Rap 1 as potential targets of vasoactive intestinal peptide effects in the human clonic cancer cells HT29.
- Author
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Hilairet S, Janet T, Pineau N, Caigneaux E, Chadeneau C, Muller JM, and Philippe M
- Subjects
- Antibodies chemistry, Antibodies isolation & purification, Blotting, Western, Centrifugation, Density Gradient, Endosomes metabolism, HT29 Cells, Humans, Immunochemistry, In Situ Hybridization, Isomerism, Phosphorylation, Reverse Transcriptase Polymerase Chain Reaction, Stimulation, Chemical, rap GTP-Binding Proteins, Antineoplastic Agents, Hormonal pharmacology, GTP-Binding Proteins metabolism, Proto-Oncogene Proteins metabolism, Vasoactive Intestinal Peptide pharmacology
- Abstract
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. These Ras-related proteins in which activity was demonstrated to be regulated by PKA phosphorylation, are considered as potential modulators of the Ras / Raf / MAP kinases cascade that governs cell growth control. Our data revealed that the Rap 1a isoform is highly expressed in HT29 cells and mainly localized in a late endosomal compartment. In these cells, VIP induces Rap 1 phosphorylation and a yet unidentified modification that leads to their acidification. This latter Rap 1 acidification seems to be, at least partially, cAMP-dependent. It is concluded that in HT29 cells, Rap 1 proteins may be part of a VIP-induced signaling cascade.
- Published
- 1998
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