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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Müller, M. Flavell, D. Mckendry, R. John, J. Kerr, I. M. Stark, G. R. |
| Description | Author Affiliation: McKendry R ( Imperial Cancer Research Fund, Lincoln's Inn Fields, London, United Kingdom.); |
| Abstract | 2fTGH is a human cell line containing the selectable marker guanine phosphoribosyltransferase regulated by alpha interferon (IFN-alpha). Two IFN-alpha-unresponsive mutants were isolated previously at a low frequency (ca. 10(-8)) by selecting mutagenized 2fTGH cells in selective medium containing 6-thioguanine and IFN-alpha. By using five rounds of mutagenesis, mutants can be isolated at an appreciably higher frequency, greater than 3 x 10(-7). Five new mutants have been isolated, and all are recessive, as are the two mutants we described previously. The seven mutants are in four complementation groups (U1-U4). Since several different types of mutants unresponsive to IFN-alpha have been isolated with high frequency, related approaches may succeed with other cytokines or growth factors. Mutants in the two new complementation groups U3 and U4 are unresponsive to IFN-alpha and, surprisingly, also unresponsive to IFN-gamma. They are also partially defective in response to double-stranded RNA. These results indicate that the signaling pathways for the two types of IFN and double-stranded RNA share common components or that their function depends on common enzymes or transcription factors. IFN receptors are unaffected in mutants U3A and U4A. A major defect appears to be in the synthesis or activation of E, the transcription factor mediating the primary response to type I (alpha/beta) IFNs. Band-shift complementation assays show that U3A contains the E gamma subunit but does not contain an active E alpha subunit after treatment with IFN-alpha. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 24 |
| Volume Number | 88 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1991-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Hypoxanthine Phosphoribosyltransferase Genetics Interferon-alpha Pharmacology Interferon-beta Mutagenesis Aminacrine Analogs & Derivatives Cell Fusion Cell Line Flow Cytometry Gene Expression Regulation, Enzymologic Drug Effects Genetic Complementation Test Interferon-gamma Kinetics Mutagens Nitrogen Mustard Compounds RNA, Messenger Receptors, Immunologic Receptors, Interferon Transcription, Genetic Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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