Disease relevance of Ceacam1

• Detection of an altered form of cell-CAM 105 on rat transplantable and primary hepatocellular carcinomas [1].
• Digestion with Clostridium perfringens or Vibrio cholerae neuraminidase did not equalize pI but instead decreased the size and increased the pI of both ARH and THC cell-CAM 105 [2].
• Inhibition of ecto-ATPase by PPADS, suramin and reactive blue in endothelial cells, C6 glioma cells and RAW 264.7 macrophages [3].
• These results suggest that CD66a has tumor-suppressive activity and that Ad-CD66a is a potential therapeutic agent for prostate cancer treatment [4].
• These findings, together with our earlier report of reduced synaptosomal ecto-ATPase activity, suggest that either the corresponding in vivo ATP concentrations were reduced as a result of status epilepticus or other biochemical changes had occurred that facilitated the hydrolysis of ATP following decapitation [5].

High impact information on Ceacam1

• Cell surface localization and tissue distribution of a hepatocyte cell-cell adhesion glycoprotein (cell-CAM 105) [6].
• Fluorescence and confocal microscopy, respectively, revealed increased pericanalicular-apical membrane localization of two canalicular markers, peanut agglutinin and a 110-kDa canalicular ecto-ATPase, when hepatocyte couplets were preincubated in HCO3-/CO2-containing medium, an effect that was again blocked by colchicine [7].
• Identification of pp120, an endogenous substrate for the hepatocyte insulin receptor tyrosine kinase, as an integral membrane glycoprotein of the bile canalicular domain [8].
• The identification of pp120 as HA4 serves to link insulin action through the receptor tyrosine kinase activity to bile metabolism and raises questions pertaining to the intracellular site(s) of action of the insulin receptor [8].
• Analysis of these proteins revealed that protein kinase Calpha and the cell adhesion signaling molecule pp120 formed temporal associations with p130Cas in response to Ang II. c-Src was found to associate with p130Cas in a manner that was independent of Ang II treatment [9].

Chemical compound and disease context of Ceacam1

• We have identified a 120 kDa glycoprotein (pp120) in rat liver plasma membranes which can be phosphorylated by the insulin receptor in a cell-free system and in intact cultured hepatoma cells [10].
• The cross-linking reagent, 1,5-difluoro-2,4-dinitrobenzene, was a potent inactivator of ecto-ATPase of C6 glioblastoma, IMR-32 neuroblastoma and of a primary rat astroblast cell line (RB) [11].

Biological context of Ceacam1

• The results of this study also show that the canalicular ecto-ATPase/bile acid transport protein is phosphorylated on its cytoplasmic tail and that its phosphorylation is stimulated by activation of protein kinase C and inhibited by inhibitors of protein kinase C activation [12].
• The amino acid sequence of the ecto-ATPase from rat liver was deduced from analysis of cDNA clones and a genomic clone [13].
• In order to definitively determine whether these were two activities of a single polypeptide, we examined the possibility that transfection of cDNA for the ecto-ATPase would confer bile acid transport characteristics, as well as ecto-ATPase activity, on heterologous cells [12].
• Because the short isoform of ecto-ATPase lacks the putative sites for tyrosine- and serine-specific phosphorylation, this alternative splicing may have a major effect upon the physiological function of the enzyme [14].
• The association of ATPase activity with cell-CAM105 raises the possibility that extracellular nucleotides may play important roles in regulating cell adhesion [15].

Anatomical context of Ceacam1

• The expressed protein is glycosylated and has an apparent molecular weight (100,000) similar to that of the rat liver plasma membrane ecto-ATPase [13].
• A truncated ecto-ATPase cDNA, missing the cytoplasmic tail, was targeted correctly to the cell surface but did not confer bile acid transport activity on COS cells [12].
• A full-length clone encoding the ecto-ATPase was expressed transiently in mouse L cells and human HeLa cells [13].
• Cell-CAM105 (also named C-CAM) is a cell surface glycoprotein involved in intercellular adhesion of rat hepatocytes [16].
• The Mr and localization of cell-CAM105 in liver membranes are very similar to those of liver ecto-ATPase, an ATPase with its nucleotide-hydrolysing site localized on the outside of the cell membrane [15].

Associations of Ceacam1 with chemical compounds

• The insulin receptor possesses tyrosine kinase activity which is thought to mediate the biological effects of insulin upon target cells. pp120 is a liver-specific glycoprotein of apparent molecular size of 120 kDa that is phosphorylated on tyrosine residues by the receptors for insulin, insulin-like growth factor-I, and epidermal growth factor [14].
• Since the mural trophoblast cells are the first to adhere to the uterine luminal epithelium during the onset of implantation and subsequently invade the uterine stroma, we suggest that the apparent downregulation of cell-CAM 105 in the mural trophoblast cells might be linked to the acquisition of trophoblast invasiveness [17].
• In contrast, although dexamethasone elevated GP 110 in fetal rat livers, none of the other marker proteins was significantly affected [18].
• Immunoprecipitation analysis of PHC induced by ethionine or diethylnitrosamine and choline-deficient diet showed that one of four PHC was expressing an altered form of cell-CAM 105 with the more basic pI characteristic of the THC form of this molecule [1].
• Bile acid transport activity was completely abrogated in cells transfected with the T502A, S503A mutant cDNA and was retained but altered in kinetic characteristics in cells transfected with the Y488F mutant cDNA, even though both of these constructs conferred ecto-ATPase activity to the same extent as the wild type cDNA [19].

Enzymatic interactions of Ceacam1

• In the present report, we have demonstrated in a cell-free system that solubilized epidermal growth factor receptors can phosphorylate tyrosine residues in pp120 [10].

Other interactions of Ceacam1

• CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes [20].
• Identification of the bile canalicular cell surface molecule GP110 as the ectopeptidase dipeptidyl peptidase IV: an analysis by tissue distribution, purification and N-terminal amino acid sequence [21].
• 5' progressive deletion and block substitution analyses revealed that the three proximal Sp1 boxes (boxes 3, 5, and 6) are required for basal transcription of the pp120 gene [22].
• For example, angiotensin II has been reported to induce the tyrosine phosphorylation of the gamma-isoform of phospholipase C, pp120, pp125FAK, and members of the janus kinase/signal transducer and activator of transcription pathway [23].
• Asialoglycoprotein receptor and 110,000 Mr glycoprotein, denoted GP 110, representing the sinusoidal and bile canalicular domains, respectively, were quantitated using the immunoblot method [18].

Analytical, diagnostic and therapeutic context of Ceacam1

• Using the reverse transcriptase/polymerase chain reaction, we isolated cDNA clones complementary to rat liver mRNA encoding pp120/ecto-ATPase [14].
• First, in Western immunoblots, two anti-cell-CAM105 monoclonal antibodies cross-reacted with the purified ecto-ATPase [15].
• Molecular cloning and expression of a new rat liver cell-CAM105 isoform. Differential phosphorylation of isoforms [24].
• Immunofluorescence analysis of normal rat tissues indicated that cell-CAM 105 was also present in the brush border of the small intestine and a subset of tubules in the kidney, raising the possibility that THC cells were expressing an isoform normally found in nonhepatic tissues [1].
• Immunoprecipitation of detergent extracts from radioiodinated hepatocytes with anti-THC antisera raised in rabbits by four immunizations with THC cells showed that six THC lines which were negative when stained by indirect immunofluorescence with MAb 362.50 expressed sufficient levels of cell-CAM 105 to induce precipitating antibodies [1].

References