Transformation by the v-fms oncogene product: role of glycosylational processing and cell surface expression.
The effect of glycosylational-processing inhibitors on the synthesis, cell surface expression, endocytosis, and transforming function of the v-fms oncogene protein (gp140fms) was examined in McDonough feline sarcoma virus-transformed Fischer rat embryo (SM-FRE) cells. Swainsonine (SW), a mannosidase II inhibitor, blocked complete processing, but an abnormal v-fms protein containing hybrid carbohydrate structures was expressed on the cell surface. SW-treated SM-FRE cells retained the transformed phenotype. In contrast, two glucosidase I inhibitors (castanospermine [CA] and N-methyl-1-deoxynojirimycin [MdN]) blocked carbohydrate remodeling at an early stage within the endoplasmic reticulum and prevented cell surface expression of v-fms proteins. CA-treated SM-FRE cells reverted to the normal phenotype. Neither SW, CA, nor MdN affected either endocytosis or the tyrosine kinase activity associated with the v-fms gene product in vitro. These results demonstrate the necessity of carbohydrate processing for cell surface expression of the v-fms gene product and illustrate the unique ability to modulate the transformed state of SM-FRE cells with the glycosylational-processing inhibitors CA and MdN.
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000378:metabolism; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004705:Endocytosis; D005786:Gene Expression Regulation / Q000187:drug effects; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007212:Indolizines; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D051381:Rats; D012190:Retroviridae / Q000235:genetics*; D005253:Sarcoma Viruses, Feline / Q000235:genetics*; D017026:Swainsonine; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D000470:Alkaloids; D005944:Glucosamine; D007212:Indolizines; D009856:Oncogene Proteins, Viral; D011505:Protein-Tyrosine Kinases; D017026:Swainsonine; C037806:castanospermine; D054836:Indolizidines; C033424:N-methyldeoxynojirimycin