| Abstract: |
To determine the functional role of the two isoforms of Fcγ, RIII (CD16) (IIIA, IIIB), the signal transduction capabilities of wild-type and mutant forms of these receptors were analyzed in transfected lymphoid, myeloid, and fibroblastic cell lines. Functional reconstitution of receptor signalling was observed in hematopoietic T and mast cells, and was absent in nonhematopoietic (CHO) cells. FcγRIIIA, a hetero-o[igomeric receptor composed of a ligand-binding subunit α and dimeric γchains, generated both proximal and distal responses in Jurkat and P815 cells, typical of what is seen in natural killer cells and macrophages upon receptor activation. In contrast, FcγRIIIB, which is normally attached to the cell surface via a glycosyl-phosphatidylinositol anchor, was incapable of transducing signals. After crosslinking, Fcγ, RIIIA signalling was dependent only upon the γ, chain. FcγRIIIA chimeras in which the α subunit transmembrane and cytoplasmic domains were substituted with the corresponding γchain sequences functioned as well as wildtype hetero-oligomeric receptors. These data indicate that the ability of the FcγRIIIA complex to activate the appropriate pathways for cell activation is cell-type restricted and independent of the transmembrane and cytoplasmic domains of the c subunit. The presence of the 3/chain is responsible for the assembly of, as well as the signal transduction by, the functional cell surface complex. © 1992, Rockefeller University Press., All rights reserved. |
| Keywords: |
signal transduction; controlled study; human cell; nonhuman; t lymphocyte; t-lymphocytes; animal cell; animal; cells, cultured; gene expression; transfection; chimera; lymphocyte activation; genetic transfection; fibroblast; fc receptor; receptors, igg; bone marrow cell; ligand binding; mutant; antigens, differentiation; cho cell; cho cells; lymphoid cell; mast cell; mast cells; calcium mobilization; gamma globin; receptors, fc; phosphatidylinositol; phosphatidylinositols; immunoglobulin structure; immunoglobulin fc fragment; protein-tyrosine kinase; phospholipase c; precipitin tests; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; hamsters; phosphatidylinositol 4,5-diphosphate
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