Carcinoembryonic antigen induces signal transduction in Kupffer cells.
Carcinoembryonic antigen (CEA), an intercellular adhesion molecule and a mediator of hepatic metastasis, is processed by an 80 kDa receptor on murine and human Kupffer cells in the liver. Activation of rat Kupffer cells in vitro by CEA via the 80 kDa receptor produced cytokines IL-1alpha and TNF-alpha which involved tyrosine phosphorylation. The peak response of TNF-alpha was 5.6 times greater than the corresponding IL-1alpha response and was associated with enhanced tyrosine phosphorylation of 108 and 125 kDa proteins. Lipopolysaccharide (LPS) treatment, on the other hand, phosphorylated two major proteins with MW of 93 and 119 kDa associated with the loss of phosphorylation from a 125 kDa protein. Results demonstrate that CEA-induced IL-1alpha and TNF-alpha production involves tyrosine phosphorylation and the signaling in CEA treated cells is different than that seen with LPS stimulation.
Gangopadhyay
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A
Department of Surgery, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Lazure
D A
DA
Thomas
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P
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000302:isolation & purification / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000737:chemistry; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008113:Liver Neoplasms / Q000737:chemistry / Q000556:secondary; D008297:Male; D051379:Mice; D008970:Molecular Weight; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; D007375:Interleukin-1; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C065686:carcinoembryonic antigen binding protein, human; D019000:Phosphotyrosine