title: EGF receptor-associated DNA-nicking activity is due to a Mr-100,000 dissociable protein.
abstract: 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.
authors.forename: M
authors.initials: M
authors.lastname: Basu
authors.forename: K
authors.initials: K
authors.lastname: Frick
authors.forename: A
authors.initials: A
authors.lastname: Sen-Majumdar
authors.forename: C D
authors.initials: CD
authors.lastname: Scher
authors.forename: M
authors.initials: M
authors.lastname: Das
mesh_terms: D004264:DNA Topoisomerases, Type I / Q000032:analysis*; D066246:ErbB Receptors; D006801:Humans; D008970:Molecular Weight; D011494:Protein Kinases / Q000032:analysis; D011505:Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000032:analysis*
chemical_list: D011956:Receptors, Cell Surface; D011494:Protein Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D004264:DNA Topoisomerases, Type I