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.

A short isoform of carcinoembryonic-antigen-related rat liver cell-cell adhesion molecule (C-CAM/gp110) mediates intercellular adhesion. Sequencing and recombinant functional analysis.

Rat liver cell-cell adhesion molecule (C-CAM) is a type I transmembrane glycoprotein belonging to the immunoglobulin (Ig)-superfamily. Within this family it is related to the carcinoembryonic antigen (CEA) proteins. C-CAM, previously known as gp110, cell-CAM 105, HA4/pp120 or ecto-ATPase, is a highly glycosylated protein with an apparent M(r) or 100,000-115,000 and an isoelectric point of 3-3.5. It was analysed as a molecule that stimulates reaggregation of isolated hepatocytes. So far three different isoforms have been cloned. Only the isoform with a long intracellular tail (71 amino acids), C-CAM1, was shown to be involved in intercellular adhesion. C-CAM2, an isoform with only 10 cytoplasmic amino acids and a slightly different N-terminal Ig-like loop did not function as an adhesion molecule. In this study we show the existence of another short C-CAM isoform (C-CAM2a), which is an alternatively spliced product of the C-CAM1 gene. Like C-CAM2, it has a short cytoplasmic tail, but in the extracellular region it is identical to C-CAM1. To investigate whether C-CAM2a can function as an adhesion molecule, we stably expressed the corresponding cDNA in Chinese hamster ovary (CHO) cells. In these cells, we detected a specific increase of intercellular adhesion, indicating that, in contrast to the other short isoform, C-CAM2a can induce adhesion. This adhesion is homophilic and Ca2+ independent.