Dissociation of cell division stimulating capacity for Balb-c-3T3 from the insulin-like activity in human serum.
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Biomedical subjects
Publications and source records attributed to C D Scher.
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The temperature-sensitive early mutant, ts(*)101, was characterized during productive infection in monkey cells, and the results are presented in an accompanying paper. This paper demonstrates that although 101 mutant virions adsorb normally to confluent Balb/3T3 mouse cells at both permissive (33 C) and restrictive (38.5 C) temperatures, T antigen synthesis and transformation, abortive and stable, are inhibited at both temperatures (host-range inhibition). T antigen synthesis is temperature sensitive, whereas abortive and stable transformation are not. Clones of 101-transformed Balb/3T3 cells were isolated, and virus was rescued from all clones at both permissive and restrictive temperatures. The rescued virus was as temperature sensitive as the original transforming 101 virions.
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The receptor for epidermal growth factor (EGF) is a single-chain transmembrane polypeptide of relative molecular mass (Mr) 170,000 (170K) which has been implicated in the regulation of both normal and abnormal cell proliferation. It has an externally facing EGF-binding domain and a cytoplasmically facing tyrosine-specific protein kinase site. Although the receptor has been well characterized, the mechanism by which it transmits the growth stimulatory signal from the plasma membrane to the nucleus is unclear. EGF binding to cells has been shown to enhance topoisomerase activity within the cells. Topoisomerases catalyse the interconversion of topological isomers of DNA and thus may influence replication and transcription. Mroczkowski et al. reported that purified EGF receptors of both human and murine origin can nick supercoiled double-stranded (ds) DNA in an ATP-dependent fashion, an activity related to those of topoisomerases. Another related tyrosine kinase, pp60src, has also been reported to have a similar DNA-nicking activity. We have now characterized the EGF receptor-associated DNA-nicking activity by sucrose gradient centrifugation. Our results, presented here, indicate that the DNA-nicking activity is not intrinsic to the EGF receptor, but is found in a distinct molecular species.