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