Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185 |
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| Authors: | C I Bargmann M C Hung R A Weinberg |
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| Affiliation: | 1. Whitehead Institute for Biomedical Research 9 Cambridge Center Cambridge, Massachusetts 02142 USA;2. Department of Biology Massachusetts Institute of Technology Cambridge, Massachusetts 01239 USA;1. VTT Technical Research Centre of Finland, P.O. Box 1300, FI-33101 Tampere, Finland;2. Tampere University of Technology, Korkeakoulunkatu 6, 33720 Tampere, Finland;3. ENEA/CREATE/University of Naples Federico II, 80125 Naples, Italy;1. Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;2. Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;3. The Institute of Experimental and Clinical Pharmacology and Toxicology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;1. Institute of Cytology RAS, St. Petersburg, Russia;2. INSERM UMR866, University of Burgundy, Dijon, France;1. Department of Molecular & Integrative Physiology, University of Michigan Medical School, 7744 Medical Science Building II, 1301 E. Catherine, Ann Arbor, MI 48109, United States;2. Department of Medicine, University of Michigan Medical School, 7744 Medical Science Building II, 1301 E. Catherine, Ann Arbor, MI 48109, United States;3. Ann Arbor Health System VA Medical Center, United States |
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| Abstract: | The neu oncogene, which is frequently activated in neuro- and glioblastomas of BDIX rats, was originally identified in the NIH 3T3 focus-forming assay. cDNA clones of the normal and transforming alleles of neu have been isolated. When these clones are inserted into the expression vector pSV2, they direct the synthesis of p185, the neu gene product. The transforming cDNA clone yields foci when transfected onto a NIH 3T3 monolayer, but the normal cDNA does not. The construction of in vitro recombinants between the normal and transforming cDNAs has allowed the determination of the mutation responsible for the activation of the neu proto-oncogene. A single point mutation changes a valine in the transmembrane domain of the predicted protein product insert to a glutamic acid. The DNAs from four independent cell lines containing activated neu oncogenes contain the identical mutation at this position. |
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