Appropriate glycosylation of the fms gene product is a prerequisite for its transforming potency.
Processing inhibitors of N-linked glycans were used to determine whether correct glycosylation of the oncogene product gp140v-fms, encoded by the McDonough strain of feline sarcoma virus (SM-FeSV), is required to maintain the oncogenic properties of v-fms. SM-FeSV-transformed cells treated with the glucosidase-I inhibitors N-methyldeoxynojirimycin (MdN) or castanospermine synthesized predominantly a gp125v-fms species which had a normal half life. The molecule was transported to the plasma membrane and exhibited normal kinase activity as determined by autophosphorylation. However, although no significant change in cell morphology of the SM-FeSV-transformed cells was observed in the presence of castanospermine, growth of these cells became strictly serum-dependent. In addition, growth in soft agar was drastically retarded despite the presence of 10% calf serum, indicating that the transformed properties of the cells were altered. In contrast, swainsonine, an inhibitor of the processing alpha-mannosidase-II, had no effect. Cells transformed by the Snyder Theilen strain of FeSV were used to demonstrate that the altered proliferative properties were directly linked to the modified structure of the fms gene product. Our data suggest that the extracellular domain of gp140v-fms plays a role in regulating cell proliferation.
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002415:Cats; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004622:Embryo, Mammalian; D005796:Genes; D005814:Genes, Viral; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D007212:Indolizines; D007668:Kidney; D009857:Oncogenes; D011499:Protein Processing, Post-Translational; D051381:Rats; D012190:Retroviridae / Q000235:genetics*; D012191:Retroviridae Proteins / Q000235:genetics*; D017026:Swainsonine; D014764:Viral Proteins / Q000235:genetics*; D054836:Indolizidines
D000470:Alkaloids; D006026:Glycoside Hydrolases; D007212:Indolizines; D012191:Retroviridae Proteins; D017026:Swainsonine; D014764:Viral Proteins; C037806:castanospermine; D054836:Indolizidines