Altered glycosylation of the env-sea oncoprotein inhibits intracellular transport and transformation.
The transforming gene product of the S13 avian erythroblastosis virus, env-sea, is a member of the growth factor receptor class of tyrosine kinases. The env-sea precursor protein gp155env-sea is proteolytically processed into the mature cleavage products gp85env and gp70env-sea, which are subsequently terminally glycosylated and transported to the cell surface. Previous studies have shown that the abnormal glycosylation of gp155env-sea induced by the carbohydrate processing inhibitor castanospermine blocks the proteolytic cleavage of gp155env-sea and impairs its transforming ability. We have shown recently that an uncleaved but fully glycosylated sea-encoded protein retains the ability to transform chicken embryo fibroblasts, indicating that proteolytic processing is not essential for transformation by the env-sea tyrosine kinase. To address the question of how castanospermine blocks transformation by env-sea, differential sucrose gradient centrifugation was performed on env-sea-transformed cells treated with the inhibitor. This report shows that no surface forms of env-sea could be detected in inhibitor-treated cells, suggesting that castanospermine acts by blocking the transport of sea-encoded proteins to the cell surface.
Crowe
A J
AJ
Department of Microbiology, State University of New York, Stony Brook 11794.
Hayman
M J
MJ
D001355:Alpharetrovirus; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002461:Cell Line, Transformed / Q000187:drug effects; D002499:Centrifugation, Density Gradient; D002642:Chick Embryo; D006031:Glycosylation; D007212:Indolizines / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000187:drug effects; D054836:Indolizidines
D007212:Indolizines; D009856:Oncogene Proteins, Viral; D011505:Protein-Tyrosine Kinases; C055694:env-sea oncogene protein, Avian Erythroblastosis Retrovirus; C037806:castanospermine; D054836:Indolizidines