Carcinoembryonic antigens: alternative splicing accounts for the multiple mRNAs that code for novel members of the carcinoembryonic antigen family.

Abstract

Abstract. The recent cloning of complete cDNAs encoding carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen has revealed the existence of a new gene family belonging to the immunoglobulin gene superfamily. We have reported the isolation of a partial CEA cDNA and of L-cell transfectant cell lines that express human antigens cross-reactive with commercial antibodies directed to native CEA (Kamarck, M., J. Elting, J. Hart, S. Goebel, P. M. M. Rae, J. Nedwin, and T. Barnett. 1987. Proc. Natl. Acad. Sci. USA. 84:5350-5354). In this study, we describe the identification and cloning of 3.9-, 3.7-, 2.2-, and 1.8-kb cDNAs and a 23-kb genomic transcription unit, which code for new members of the CEA gene family. DNA sequence analysis of these cloned DNAs establishes the existence of a set of four alternatively spliced mRNAs which are expressed in several tumor cell lines, in human fetal liver, and in L-cell transfectants. Deduced amino acid sequences of the encoded isoantigens show extensive similarity to CEA and nonspecific cross-reacting antigens, but in addition demonstrate transmembrane and cytoplasmic domains. We designate members of this antigen family transmembrane' CEAs. The transmembrane CEA isoantigens share general structural characteristics with members of the immunoglobulin gene superfamily and can be specifically compared to the cell adhesion molecules, N-CAM (neural cell adhesion molecule) and MAG (myelin-associated glycoprotein).

Genomic organization, splice variants and expression of CGM1, a CD66‐related member of the carcinoembryonic antigen gene family

“…In CGMlc, the first cytoplasmic domain exon (Cytl) is spliced out, thus creating a shift in the reading frame and leading to a different amino acid sequence. Sequences similar to the Cytl exon of CGMl are also found in human [BGPa or TM-1 CEA and BGPb or TM-2 CEA Barnett et al, 1989)] and rodent BGP splice variants [ectoATPase (Lin and Guidotti, 1989)l. Deletion of this exon in BGP splice variants (BGPc, BGPd) also results in shorter cytoplasmic domains, although with a different sequence compared to CGMlc, since the sequence following the Cytl region in BGP is not homologous to Cyt2, Cyt3 or Cyt4.…”

“…NCA, CGM6) or have a hydrophobic transmembrane region (BGP). For BGP as well as for its rat (ecto ATPase) and mouse homologues (mmCGM1/2), isoforms have been described which differ in the length of their cytoplasmic domains (Barnett et al, 1989;Lin and Guidotti, 1989;McCuaig et al, 1992;Culic et al, 1992). The intracellular domains of human and rat BGP isoforms are phosphorylated (Afar et al, 1992;Culic et al, 1992).…”

The CEACAM1-mediated apoptosis pathway is activated by CEA and triggers dual cleavage of CEACAM1

“…It is composed of four extracellular domains and a long (CEACAM1-4L) or short (CEACAM1-4S) cytoplasmic domain which are encoded by alternative splicing (Hinoda et al, 1988;Barnett et al, 1989). The cytoplasmic domains of CEACAM1 are phosphorylated at their serine residues (Edlund et al, 1998;Fournes et al, 2001) and bind to calmodulin (Edlund et al, 1996).…”

Association of biliary glycoprotein with protein tyrosine phosphatase SHP-1 in malignant colon epithelial cells

“…Bgp is well conserved throughout evolution. The human, mouse and rat Bgp proteins exhibit very similar extracellular domains (Barnett et al, 1989;Lin and Guidotti, 1989;O È brink, 1991;McCuaig et al, 1992). However, their most conserved feature is in their cytoplasmic domains, which exhibit 77 ± 92% similarity at the amino acid level.…”

“…However, their most conserved feature is in their cytoplasmic domains, which exhibit 77 ± 92% similarity at the amino acid level. Bgp proteins possess cytoplasmic domains of either 10 or 71 (73 in mouse) amino acids which are produced by alternative splicing of a conserved 53 bp exon (Barnett et al, 1989;Ne dellec et al, 1995). They are mainly expressed in epithelial cells of the gastro-intestinal tract, endothelial cells and hematopoietic cells, particularly B cells, neutrophils and macrophages (Hinoda et al, 1988;Barnett et al, 1989;O È brink, 1991;Coutelier et al, 1994;Ne dellec et al, 1995).…”