DEMONSTRATION OF ADHESION ACTIVITY OF THE SOLUBLE IG-DOMAIN PROTEIN C-CAM4 BY ATTACHMENT TO THE PLASMA-MEMBRANE

The carcinoembryonic antigen (CEA) family is a large group of proteins with immunoglobulin (Ig)-like structures. The membrane-associated CEA -family proteins have been shown to mediate intercellular adhesion. In addition to these membrane-associated proteins, several secreted CELL -like proteins, such as C-CAM4, PSG1b, and PSG11s, have also been iden tified. The functions of these soluble proteins are not clear because they cannot support intercellular adhesion like the membrane-associate d proteins can. A fundamental question important for understanding the functions of these soluble proteins is whether they can interact in a hemophilic fashion as do many of their membrane-associated homologues . me found that the hemophilic interactions between these soluble prot eins were too weak to be detected by solution binding assays, This is not unexpected because interactions between adhesion molecules are usu ally transient and weak to allow for control of association and dissoc iation. By expressing these soluble CEA-family proteins, C-CAM4, PSG1b , and PSG11s, as membrane-anchored forms, we showed that C-CAM4 could mediate intercellular adhesion, whereas PSG1b and PSG11s, despite thei r 52 % identity to C-CAM4, could not. These results suggest that C-CAM 4, but not PSG1b and PSG11s, can probably form homodimers. Thus, these secretory CEA-family members most likely have different interaction m echanisms, i.e., C-CAM4 might function as dimers, while PSGs might fun ction as monomers. (C) 1998 Academic Press.