| First Author | Dighe AS | Year | 1993 |
| Journal | J Biol Chem | Volume | 268 |
| Issue | 14 | Pages | 10645-53 |
| PubMed ID | 8387525 | Mgi Jnum | J:74621 |
| Mgi Id | MGI:2158880 | Doi | 10.1016/s0021-9258(18)82246-3 |
| Citation | Dighe AS, et al. (1993) Inhibition of cellular responsiveness to interferon-gamma (IFN gamma) induced by overexpression of inactive forms of the IFN gamma receptor. J Biol Chem 268(14):10645-53 |
| abstractText | Herein, we report that overexpression of either human or murine interferon-gamma (IFN-gamma) receptors lacking their entire intracellular domains in cells bearing functionally active IFN gamma receptors ablates responsiveness to homologous ligand in a dominant negative manner. Unresponsiveness could also be induced in murine cells overexpressing murine IFN gamma receptor mutants that either lack 39 COOH-terminal amino acids or contain an alanine substitution for a functionally critical tyrosine. Overexpression of the full-length receptor did not alter cellular responsiveness to IFN gamma. The inhibitory activities of the receptor mutants were dose-dependent, generalizable to a variety of cellular responses, and specific. Cells expressing 100:1 ratios of mutant to wild-type receptor were unresponsive to IFN gamma even at doses 30,000 times greater than that required to induce a maximal response in wild-type cells. These results provide an example of a dominant negative mutation that effects the complete inactivation of a transmembrane receptor lacking a kinase domain and suggest a more general utility for dominant negative mutations in the study of cytokine receptor function. |
