Post-translational modifications of the env-sea oncogene product: the role of proteolytic processing in 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-sea and gp70env-sea which are subsequently terminally glycosylated. Previous studies have shown that the abnormal glycosylation of gp155env-sea which takes place in the presence of the inhibitor castanospermine inhibits the proteolytic cleavage of gp155env-sea and blocks its transforming ability. To define a role for proteolytic processing of env-sea in transformation, we have introduced mutations at the protease recognition site which efficiently block cleavage without affecting the biosynthesis or transport of the resulting uncleaved protein. We show here 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.
Crowe
A J
AJ
Department of Microbiology, State University of New York, Stony Brook 11794.
Hayman
M J
MJ
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D015686:Gene Products, env / Q000502:physiology; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006031:Glycosylation; D007212:Indolizines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013696:Temperature; D054836:Indolizidines
D015686:Gene Products, env; D006026:Glycoside Hydrolases; D007212:Indolizines; D009856:Oncogene Proteins, Viral; D011505:Protein-Tyrosine Kinases; C055694:env-sea oncogene protein, Avian Erythroblastosis Retrovirus; C037806:castanospermine; D054836:Indolizidines