Cell transformation potential of a HER2 transmembrane domain deletion mutant retained in the endoplasmic reticulum.
The HER2 (c-erbB-2) gene encodes a protein, p185HER2, which possesses all of the structural characteristics and functional properties of a growth factor receptor, although its ligand has not yet been well characterized. HER2 is the human homolog of the rat proto-oncogene neu and is closely related to the gene encoding the epidermal growth factor receptor. Amplification of this gene and overexpression have been found to be a prognostic criterion for a 30% subpopulation of human breast cancer patients. In this study, we investigated the role of the transmembrane-spanning sequence in the biosynthesis and localization of p185HER2. A truncation mutant lacking the cytoplasmic and transmembrane domains was glycosylated and efficiently secreted. However, a mutant lacking only the transmembrane-spanning sequence was incompletely glycosylated and failed to reach the cell surface. Unexpectedly, although this deletion mutant was retained in the endoplasmic reticulum membrane, it was still able to transform NIH 3T3 cells when expressed at high levels.
Genetech, Inc., South San Francisco, California 94080.
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RM
Hudziak
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A
Ullrich
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002462:Cell Membrane / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D002872:Chromosome Deletion; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D011519:Proto-Oncogenes; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D014415:Tunicamycin / Q000494:pharmacology
D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D014415:Tunicamycin; C000715470:MAS1 protein, human