C-CAM-mediated adhesion leads to an outside-in dephosphorylation signal.

The rat cell-cell adhesion molecule C-CAM, a member of the carcinoembryonic antigen family, was shown to be expressed in various isoforms, differing in the length of the cytoplasmic domain. The long isoform C-CAML inhibits the growth of different malignant cells. Several studies suggest that it is involved in the mechanism of signal transduction. So far no direct correlation between C-CAM function and C-CAM phosphorylation has been reported. In the present study we addressed the question of whether C-CAM-mediated adhesion is accompanied by changes in phosphorylation of the cytoplasmic domain of C-CAM. It was demonstrated that C-CAML is constitutively phosphorylated in adherent growing cells as well as in cells growing in suspension. In contrast, C-CAML-mediated cell aggregation is accompanied by a 40% reduction in C-CAML phosphorylation compared with nonaggregated cells. The same dephosphorylation was achieved by antibody-induced clustering of C-CAML in the plasma membrane. Phosphorylation and dephosphorylation indicate a C-CAM-mediated outside-in signalling induced by cell-cell adhesion.