Genetic analysis of interferon and other mammalian signaling pathways.
Stark GR.
Lerner Research Institute, Cleveland Clinic Foundation, Ohio, USA.
Systematic forward genetics, so powerful for analyzing pathways in haploid organisms, has contributed much less to our understanding of diploid mammalian cells. With Ian Kerr, we have used regulated expression of selectable markers in heavily mutagenized cells to isolate mutant mammalian cell lines defective in eight different proteins required for interferon signaling. These cells have been valuable in studying the roles of the deleted Janus Kinase (JAK), signal transducer and activator of transcription (STAT), and receptor proteins in interferon and other signaling pathways. Mutant cells defective in the induction of class II major histocompatibility complex (MHC) antigens by interferon-gamma or in repressing interferon-regulated genes have also been obtained. More recently, mutant cells unresponsive to double-stranded RNA, tumor necrosis factor alpha (TNF-alpha), or interleukin-1 (IL-1) have been isolated and characterized and a mutant line defective in expressing the tumor suppressor protein p53 has also been obtained. Systematic forward genetics can now be applied more easily to mammalian cells, to help elucidate signaling pathways.
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PMID: 10941415 [PubMed - indexed for MEDLINE]