Evidence that the putative COOH-terminal signal transamidase involved in glycosylphosphatidylinositol protein synthesis is present in the endoplasmic reticulum.
Nascent proteins destined to be processed to a glycosylphosphatidylinositol (GPI)-anchored membrane form contain NH2-terminal and COOH-terminal signal peptides. The first directs a nascent protein into the endoplasmic reticulum; the second peptide targets the protein to a putative COOH-terminal signal transamidase where cleavage of the peptide and addition of the GPI anchor occur. We recently showed that ATP hydrolysis is required for maturation of GPI proteins at a stage prior to transamidation. Here we show that one of the ATP-requiring proteins involved in processing of GPI-anchored proteins in the endoplasmic reticulum is the immunoglobulin heavy chain binding protein (BiP; GRP 78). This and related findings indicate that GPI transamidase is localized in the endoplasmic reticulum.
Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110.
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Amthauer
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Kodukula
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Gerber
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Udenfriend
D000217:Acyltransferases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001413:Bacillus thuringiensis / Q000378:metabolism; D020126:Brefeldin A; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D014162:Transfection
D002352:Carrier Proteins; D003517:Cyclopentanes; D000091342:Endoplasmic Reticulum Chaperone BiP; D017261:Glycosylphosphatidylinositols; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D011506:Proteins; D020126:Brefeldin A; D000255:Adenosine Triphosphate; D000217:Acyltransferases; C081007:COOH-terminal signal transamidase; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase