title: Carcinoembryonic antigen-related cell adhesion molecule 1 expression and signaling in human, mouse, and rat leukocytes: evidence for replacement of the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked proteins in human leukocytes.
abstract: Carcinoembryonic Ag-related cell adhesion molecule 1 (CEACAM1), the primordial carcinoembryonic Ag gene family member, is a transmembrane cell adhesion molecule expressed in leukocytes, epithelia, and blood vessel endothelia in humans and rodents. As a result of differential splicing, CEACAM1 occurs as several isoforms, the two major ones being CEACAM1-L and CEACAM1-S, that have long (L) or short (S) cytoplasmic domains, respectively. The L:S expression ratios vary in different cells and tissues. In addition to CEACAM1, human but not rodent cells express GPI-linked CEACAM members (CEACAM5-CEACAM8). We compared the expression patterns of CEACAM1-L, CEACAM1-S, CEACAM6, and CEACAM8 in purified populations of neutrophilic granulocytes, B lymphocytes, and T lymphocytes from rats, mice, and humans. Human granulocytes expressed CEACAM1, CEACAM6, and CEACAM8, whereas human B lymphocytes and T lymphocytes expressed only CEACAM1 and CEACAM6. Whereas granulocytes, B cells, and T cells from mice and rats expressed both CEACAM1-L and CEACAM1-S in ratios of 2.2-2.9:1, CEACAM1-S expression was totally lacking in human granulocytes, B cells, and T cells. Human leukocytes only expressed the L isoforms of CEACAM1. This suggests that the GPI-linked CEACAM members have functionally replaced CEACAM1-S in human leukocytes. Support for the replacement hypothesis was obtained from experiments in which the extracellular signal-regulated kinases (Erk)1/2 were activated by anti-CEACAM Abs. Thus, Abs against CEACAM1 activated Erk1/2 in rat granulocytes, but not in human granulocytes. Erk1/2 in human granulocytes could, however, be activated by Abs against CEACAM8. We demonstrated that CEACAM1 and CEACAM8 are physically associated in human granulocytes. The CEACAM1/CEACAM8 complex in human cells might accordingly play a similar role as CEACAM1-L/CEACAM1-S dimers known to occur in rat cells.
authors: Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors: Bernhard B
authors: BB
authors: Singer
authors: Inka
authors: I
authors: Scheffrahn
authors: Robert
authors: R
authors: Heymann
authors: Kristmundur
authors: K
authors: Sigmundsson
authors: Robert
authors: R
authors: Kammerer
authors: Björn
authors: B
authors: Obrink
mesh_terms: D017398:Alternative Splicing; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D003593:Cytoplasm / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006098:Granulocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; C069847:CD66 antigens; C504117:CEACAM6 protein, human; C504120:CEACAM8 protein, human; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D020033:Protein Isoforms