The order of processing events in mouse mammary tumor virus envelope protein maturation: implications for the location of the glucocorticoid-regulated step.
Treatment of the W7MG1 mouse T lymphoma cell line with glucocorticoid stimulates directly or indirectly two observable steps in the processing of mouse mammary tumor virus (MMTV) envelope glycoprotein precursor Pr74: cleavage of Pr74 to yield the mature glycoprotein products gp52 and gp33, and processing of the N-linked oligosaccharides to endoglycosidase H (endo H)-resistant forms found on the mature products but not on the precursor. Therefore, the primary hormone-regulated event in this pathway must occur at or before the point where MMTV envelope proteins become endo H resistant. Pulse-chase analyses identified a novel endo H-resistant 80-kDa species (designated gp80) as a processing intermediate. Therefore, in contrast to conclusions drawn for the envelope proteins of several other retroviruses, proteolytic cleavage of MMTV envelope proteins occurs after acquisition of endo H resistance. Also, proteolytic cleavage cannot be the primary hormone-regulated step. Second, inhibition of mannosidase II by the drug swainsonine did not prevent Pr74 from being proteolytically processed, thus demonstrating that conversion of oligosaccharide chains from endo H-sensitive to -resistant forms was not a prerequisite for proteolytic cleavage. Therefore, the requisite hormone-regulated event in MMTV glycoprotein processing must precede both acquisition of endo H resistance and proteolytic cleavage. This places the regulated event in the endoplasmic reticulum or early Golgi.
Corey
J L
JL
Department of Pathology, University of Southern California, Los Angeles 90033.
Stallcup
M R
MR
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D007700:Kinetics; D008324:Mammary Tumor Virus, Mouse / Q000378:metabolism*; D008361:Mannosidases / Q000037:antagonists & inhibitors; D051379:Mice; D011499:Protein Processing, Post-Translational; D017026:Swainsonine; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000470:Alkaloids; D000957:Antigens, Viral, Tumor; D005938:Glucocorticoids; D014759:Viral Envelope Proteins; C040612:glycoprotein 52 antigen, Mouse mammary tumor virus; D008361:Mannosidases; C038829:mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase; D010450:Endopeptidases; D017026:Swainsonine