Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown previously that CaBP2, the rat analog of the murine protein ERp72, and CaBP1, the rat analogue of the hamster protein P5, represent members of the protein disulfide isomerase (PDI) family and are able to catalyze the reduction of insulin in the presence of various reductants (Nguyen Van et al., 1993). We have now examined the abilities of CaBP2 and CaBP1 to catalyze the renaturation of denatured reduced model proteins. Both CaBP2 and CaBP1 catalyzed the reappearance of the biological activity of the denatured reduced Fab fragment of a monoclonal anti-human creatine phosphokinase antibody. The reaction rate was positively correlated with the amount of CaBP2 or CaBP1 and dependent on the GSH/GSSG ratio (maximum at GSH/GSSG = 1). Peptide prolyl-cis,trans-isomerase (PPI), which catalyzed some renaturation on its own, showed synergistic effects with PDI, CaBP2, and CaBP1. No synergistic effects could be observed when the combinations CaBP2 + PDI, CaBP1 + PDI, or CaBP2 + CaBP1 were tested. Variation of [Ca2+] between 0 and 1 mM did not have any effect on the rate or amount of renaturation catalyzed by CaBP2, CaBP1, or PDI, nor were these parameters affected by the simultaneous presence of BiP or grp94. Both CaBP2 and CaBP1 catalyzed also the renaturation of denatured reduced ribonuclease AIII in a way that depended on the amounts of CaBP2 or CaBP1 and on the redox potential of the redox system used (GSH/GSSG or CSH/CSSC). PPI alone had no effect on the rate of RNase AIII renaturation and did not significantly affect renaturation catalyzed by PDI, CaBP2, or CaBP1. PDI showed a moderate but significant synergism with CaBP2, and a strong synergism with CaBP1. The results indicate that both CaBP2 and CaBP1 can catalyze the formation of disulfide bonds and protein disulfide isomerization and may thus be involved in the folding of nascent proteins in the secretory pathway. This does not exclude the possibility of additional functions of these proteins in the pre-Golgi compartments.
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PMID:Effects of CaBP2, the rat analog of ERp72, and of CaBP1 on the refolding of denatured reduced proteins. Comparison with protein disulfide isomerase. 830 May 76

The activity of BiP, the major chaperone of the endoplasmic reticulum (ER) lumen, is known to be Ca2+-regulated; however, the participation of this protein in the ER storage of the cation has not yet been investigated. Here such a role is demonstrated in human epithelial (HeLa) cells transiently transfected with the hamster BiP cDNA and incubated in Ca2+-free medium, as revealed by two different techniques. In the first, co-transfected aequorin was employed as a probe for assaying either the cytosolic of the mitochondrial free Ca2+ concentration. By this approach higher Ca2+ release responses were revealed in BiP-transfected cells by experiments in which extensive store depletion was induced either by repetitive stimulation with inositol 1,4,5-trisphosphate-generating agonists or by treatment with the Ca2+ ionophore, A23187. In the second technique the cells were loaded at the equilibrium with 45Ca, and the release of the tracer observed upon treatment with thapsigargin, a blocker of the ER Ca2+ ATPases, was larger in BiP-transfected than in control cells. The latter results were obtained also when BiP was overexpressed not via transfection but as a response to ER stress by tunicamycin. These results are sustained by increases of the ER Ca2+ storage capacity rather than by artifacts or indirect readjustments induced in the cells by the overexpression of the chaperone since (a) the exogenous and endogenous BiP were both confined to the ER, (b) the expression levels of other proteins active in the ER Ca2+ storage were not changed, and (c) effects similar to those of wild type BiP were obtained with a deletion mutant devoid of chaperone activity. The specificity of the results was confirmed by parallel 45Ca experiments carried out in HeLa cells transfected with two other Ca2+-binding proteins, calreticulin and CaBP2(ERp72), only the first of which induced increases of Ca2+ capacity. We conclude that BiP has a dual function, in addition to its chaperone role it is a bona fide ER lumenal Ca2+ storage protein contributing, under resting cell conditions, to around 25% of the store, with a stoichiometry of 1-2 moles of calcium/mole of BiP.
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PMID:BiP, a major chaperone protein of the endoplasmic reticulum lumen, plays a direct and important role in the storage of the rapidly exchanging pool of Ca2+. 938 33