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 CEA-like proteins, such as C-CAM4, PSG1b, and PSG11s, have also been identified. The functions of these soluble proteins are not clear because they cannot support intercellular adhesion like the membrane-associated proteins can. A fundamental question important for understanding the functions of these soluble proteins is whether they can interact in a homophilic fashion as do many of their membrane-associated homologues. We found that the homophilic interactions between these soluble proteins were too weak to be detected by solution binding assays. This is not unexpected because interactions between adhesion molecules are usually transient and weak to allow for control of association and dissociation. 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 their 52% identity to C-CAM4, could not. These results suggest that C-CAM4, but not PSG1b and PSG11s, can probably form homodimers. Thus, these secretory CEA-family members most likely have different interaction mechanisms, i.e., C-CAM4 might function as dimers, while PSGs might function as monomers.
Lin
S H
SH
Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. sue-hwa_lin@path.mdacc.tmc.edu
Cheng
H
H
Earley
K
K
Luo
W
W
Chou
J
J
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D002272:Carcinoembryonic Antigen / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000502:physiology; D002449:Cell Aggregation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D007074:Immunoglobulin G / Q000737:chemistry*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D018411:Spodoptera / Q000166:cytology / Q000235:genetics
D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D008565:Membrane Proteins; D011994:Recombinant Proteins; D000251:Adenosine Triphosphatases