Disease relevance of Ceacam1

• When Bgp2-transfected hamster cells were challenged with MHV-A59, MHV-JHM, or MHV-3, the Bgp2-encoded protein served as a functional MHV receptor, although with a lower efficiency than that of the MHVR glycoprotein [1].
• To investigate the interactions of these alternative MHVR glycoproteins with MHV, we expressed and purified to apparent homogeneity the extracellular domains of several murine Bgps as soluble, six-histidine-tagged glycoproteins, using a baculovirus expression system [2].
• Very little mmCGM1 was detected in the mouse brain or in cells of the susceptible mouse astrocytoma cell line DBT [3].
• We found that the three isoforms tested could serve as functional receptors for MHV-A59, although only isoforms that include the N-terminal domain of MHVR were recognized by monoclonal antibody CC1 in immunoblots or by MHV-A59 virions in virus overlay protein blot assays [4].
• Mutational analysis of the virus and monoclonal antibody binding sites in MHVR, the cellular receptor of the murine coronavirus mouse hepatitis virus strain A59 [5].

Psychiatry related information on Ceacam1

• To assess the role of receptors in the limited tissue tropism of enterotropic MHV strains, the permissiveness of MHVR- and mmCGM2-expressing cell lines and peritoneal exudate cells from BALB/c and SJL mice for MHV-RI and MHV-Y replication was determined [6].

High impact information on Ceacam1

• Forward and reverse genetics in the mouse now provide powerful novel models to elucidate the action of CEACAM family members in vivo [7].
• Transfection of the cDNA into COS-7 cells, which lack a functional MHV receptor, conferred susceptibility to infection by some MHV strains, including A59, MHV-2, and MHV-3, but not JHM [8].
• Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody [9].
• The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo [10].
• The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution [10].

Chemical compound and disease context of Ceacam1

• GAG binding by B. burgdorferi is associated with haemagglutination and we have identified a 26 kDa protein, which we have termed Bgp (Borrelia GAG-binding protein), on the basis of its ability to bind to heparin and erythrocytes [11].
• Androgen independent prostate cancer and its metastatic tumors generated in castrated TRAMP mice were also C-CAM negative [12].

Biological context of Ceacam1

• Our sequence analysis revealed that the genes encoded nine exons and spanned approx. 16-17 kb (Ceacam1) and 25 kb (Ceacam2) [13].
• There is considerable divergence in the amino acid sequences of the N-terminal domains of the proteins coded by the Bgp1 gene from that of the Bgp2-encoded protein [1].
• By polymerase chain reaction with the conserved sequences of murine CEA gene family members (mmCGM) as primers, we detected two CEA-encoding RNAs in the mouse liver [3].
• To elucidate its physiological function by targeted gene deletion, we isolated the Ceacam genes from a mouse 129 Sv/Ev library [13].
• Chimeric proteins constructed between the different murine Bgps and point mutations in the prototype MHV receptor, Bgp 1a or MHVR, were analyzed to further characterize the MAb-CC1-binding and virus-binding domains within the N terminal domain of the receptor [14].

Anatomical context of Ceacam1

• Manipulation of the Ceacam1 gene in mouse embryonic stem cells that contained the Ceacam1a allele yielded a partial knockout [15].
• As in human and rat, in the mouse Ceacam1 mRNA was highly abundant in the liver, small intestine, prostate and spleen [13].
• Expression of either of these cDNA clones in COS-7 cells rendered these cells susceptible to MHV infection, suggesting that not only mmCGM1 but also mmCGM2 serves as a receptor for MHV [3].
• Expression of the mouse hepatitis virus receptor by central nervous system microglia [16].
• Detection of the mouse hepatitis virus receptor within the central nervous system (CNS) has been elusive [16].

Associations of Ceacam1 with chemical compounds

• The soluble four-domain MHVR glycoprotein (sMHVR[1-4]) had fourfold more MHV-A59 neutralizing activity than the corresponding soluble Bgp1(b) (sBgp1(b)) glycoprotein and at least 1,000-fold more neutralizing activity than sBgp2 [2].
• We recently demonstrated that C-CAM, an epithelial-cell adhesion molecule of the immunoglobulin supergene family, could be regulated by androgen and might act as a growth repressor during differentiation of the prostatic epithelium [17].
• Nonglycosylated core MHVR proteins were made in Vac-MHVR-infected BHK-21 cells in the presence of tunicamycin by in vitro translation of MHVR mRNA in a rabbit reticulocyte cell-free system in the absence of microsomal membranes and by expression of an N-terminal deletion clone of MHVR lacking its signal peptide [18].
• C-CAM produced dose-dependent rightward and slight downward shifts of the etonitazene dose-effect curve [19].
• In addition, it was observed that higher doses of C-CAM were required to produce a shift down in the fentanyl dose-effect curve than were required to produce a shift down in the morphine dose-effect curve, which suggests that fentanyl is more efficacious than morphine [20].

Physical interactions of Ceacam1

• In this investigation, peptides corresponding to the cytoplasmic domains of C-CAM were synthesized on cellulose membranes and used to map the binding sites for 125I-labeled calmodulin [21].

Regulatory relationships of Ceacam1

• This suggests that calmodulin can regulate the functional activity of C-CAM [21].
• To investigate the functional significance of SYNCRIP in MHV replication, we expressed a full-length or a C-terminally truncated form of SYNCRIP in mammalian cells expressing the MHV receptor [22].

Other interactions of Ceacam1

• The Bgp2-mediated virus infection could not be inhibited by monoclonal antibody CC1 that is specific for the N-terminal domain of MHVR [1].
• The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail, MHVR1 is closely related to the murine CEA-related clone mmCGM1 (Mus musculus carcinoembryonic antigen gene family member) [23].
• Treatment of macrophages with DE-IFN-gamma selectively induced the expression of the cellular inducible nitric oxide synthase and the IFN-gamma-inducing factor (IGIF) but did not affect the amounts of the MHV receptor mRNA [24].
• The ascending genes include several angiogenic factors: FGF receptor 4, vascular endothelial growth factor (vEGF), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) [25].
• Recently, we demonstrated that an androgen-regulated cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer development [26].

Analytical, diagnostic and therapeutic context of Ceacam1

• In addition, we used site-directed mutagenesis to introduce selected amino acid changes into the N-terminal domains of MHVR and these chimeras and tested the abilities of these mutant glycoproteins to bind MAb CC1 and to function as MHV receptors [5].
• Using Western blotting and immunohistochemical analysis, the protein expression level and localization of CEACAM-1 were observed in hypoxic myocardium [25].
• In this study, we further explored the possibility of applying C-CAM as a potential agent for developing prostate cancer gene therapy using an adenoviral delivery system [26].
• In this study, we examined the relationship between C-CAM expression during human prostate development and neoplastic progression by immunohistochemical staining of frozen sections [27].
• Biosensor experiments were performed to determine rate and equilibrium constants of the C-CAM/calmodulin interaction [21].

References