Homophilic Intercellular Adhesion Mediated by C-CAM Is Due to a Domain 1–Domain 1 Reciprocal Binding

Wikström, Kristina; Kjellström, Gunilla; Öbrink, Björn

doi:10.1006/excr.1996.0285

Cited by 35 publications

(29 citation statements)

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“…CEACAM1 is known to mediate cell-cell adhesion by homophilic binding between its N domains [13]. Anti-CEACAM1 antibodies and soluble recombinant CEA-CAM1-Fc fusion proteins are able to mimic these interactions [11,14].…”

Section: Introductionmentioning

confidence: 99%

CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes

et al. 2005

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Granulocytes form the first and fastest line of defense against pathogenic infections. Their survival is limited by apoptosis, a process that is critical for the resolution of inflammation. Pro-apoptotic and pro-inflammatory cytokines, as well as several receptors, can alter the lifespan of granulocytes. Here we report that the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is involved in the regulation of granulocyte survival. Until now CEACAM1 is described to control cell proliferation, cell migration, tumor growth, angiogenesis and diverse leukocyte functions. However, very little is known about its role in granulocytes. We found that CEACAM1 expression in resting rat granulocytes is significantly higher than in other leukocyte subtypes. Stimulation led to a strongly increased CEACAM1 cell surface expression and to release of soluble CEACAM1. DNA fragmentation assays and annexin V staining revealed that binding of CEACAM1-specific antibodies, Fab fragments and soluble CEACAM1-Fc constructs to cell surface-expressed CEACAM1 causes a delay of spontaneous and Fas ligand (CD95L)-induced apoptosis. Tyrosine phosphorylation of CEACAM1-L, its association with SHP-1, the activation of Erk1/2 and caspase-3 appeared to be crucial for the CEACAM1-mediated anti-apoptotic effect. These findings provide evidence that CEACAM1 influences the resolution of inflammation by prolonging the survival of rat granulocytes.

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Section: Introductionmentioning

confidence: 99%

CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes

et al. 2005

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“…Because the N-terminal IgV set domain of CEACAM1 has been implicated in mediating homophilic adhesion, 7,[19][20][21][22][23] we have determined the key amino acid residues (single-letter amino acid codes used throughout) involved in such interactions using site-directed mutagenesis. The basic structure of the IgV N-terminal domain of CEACAM1 is a predicted tertiary fold of a stacked pair of ␤-pleated sheets.…”

Section: Introductionmentioning

confidence: 99%

Homophilic adhesion of human CEACAM1 involves N-terminal domain interactions: structural analysis of the binding site

Watt¹,

Teixeira

Zhou

et al. 2001

Blood

117

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“…Relatively recent studies have also shown that the ectodomain is not required for tumor suppression; the CEACAM1 a -4L cyto domain is necessary and sufficient for inhibiting tumorigenicity (24). Cell-cell adhesion, on the other hand, appears to be an activity that is mediated primarily by the N-terminal V-like domain (4,(25)(26)(27). Because all of the CEACAM1 alleles and genes have…”

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Two Variable Regions in Carcinoembryonic Antigen-related Cell Adhesion Molecule1 N-terminal Domains Located in or Next to Monoclonal Antibody and Adhesion Epitopes Show Evidence of Recombination in Rat but Not in Human

Comegys

Lin

Rand

et al. 2004

Journal of Biological Chemistry

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In this paper, we have characterized the structure, evolutionary origin, and function of rat and human carcinoembryonic antigen-related cell adhesion molecule1 (CEACAM1) multifunctional Ig-like cell adhesion proteins that are expressed by many epithelial tissues. Restriction enzyme digestion reverse transcriptase-PCR analysis identified three cDNAs encoding novel CEACAM1 N-domains. Comparative sequence analysis showed that human and rat CEACAM1 N-domains segregated into two groups differing in similarity to rat CEACAM1 a -4L and human CEACAM1. Sequence variability analysis indicated that both human and rat Ndomains possessed two variable regions, and one contained a major adhesive epitope. Recombination analysis showed that the group of rat but not human N-domains with high sequence similarity was derived at least in part by recombination. Binding assays revealed that three monoclonal antibodies with strong reactivity for the CEACAM1 a -4L N-domain showed no reactivity with CEACAM1 b -4S, an allele with a different N-domain sequence. CEACAM1 b -4S displayed adhesive activity efficiently blocked by a synthetic peptide corresponding to the adhesive epitope in CEACAM1 a -4L. Blocking analysis also showed that the adhesive epitope for rat CEACAM1 was located downstream from the equivalent human and mouse epitopes. Glycosylation analysis demonstrated O-linked sugars on rat CEACAM1 b -4S from COS-1 cells. However, this was not the alteration responsible for the lack of monoclonal antibody reactivity. When considered together with previous studies, our findings suggest an inverse relationship between functionality and amino acid sequence similarity to CEACAM1. Like IgG, the N-domain of CEACAM1 appears to tolerate 10 -15% sequence diversification without loss of function but begins to show either altered specificity or diminished functionality at higher levels.Carcinoembryonic antigen-related cell adhesion molecule1 (CEACAM1) 1 is a member of a large family of multifunctional Ig-like cell adhesion molecules (CAMs) structurally related to carcinoembryonic antigen (CEA) (2, 3). CEACAM1 from both rodents and humans is composed of an ectodomain with an N-terminal Ig V-like domain (N-domain), three Ig-like C-domains, a single transmembrane domain, and a cytoplasmic (cyto) domain that through differential splicing varies in length from 6 to 71 amino acids (4 -6). Multiple genes with unique N-domain sequences and a variety of splice variants have been reported in both rodents and humans (2, 3, 5-12). The major splice variants in rodents and humans have from 2 to 4 Ig-like domains and cyto domains with either 70 -71 (L forms) or 9 -10 amino acids (S forms) (1-3, 5, 6). In rodents, allelic variants (Ceacam1 a and 1 b ) 2 or separate genes differing in both the nucleotide and amino acid sequence of their N-terminal Ig domains (rats and mice) have also been described (1, 13).Interest in the role of CEACAM1 in cancer has blossomed since early reports showed that this gene was lost or greatly down-regulated in rodent hepatocellular ...

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Homophilic Intercellular Adhesion Mediated by C-CAM Is Due to a Domain 1–Domain 1 Reciprocal Binding

Cited by 35 publications

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CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes

CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes

Homophilic adhesion of human CEACAM1 involves N-terminal domain interactions: structural analysis of the binding site

Two Variable Regions in Carcinoembryonic Antigen-related Cell Adhesion Molecule1 N-terminal Domains Located in or Next to Monoclonal Antibody and Adhesion Epitopes Show Evidence of Recombination in Rat but Not in Human

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