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

Previously we found that in rat exocrine pancreatic cells, protein disulfide-isomerase (PDI), one of the major resident proteins in the lumen of the endoplasmic reticulum (ER) of many cells, is localized not only in the ER but also in the Golgi apparatus, secretory granules, plasma membranes, and even in the glandular lumens, despite possessing the ER retention signal KDEL (Lys-Asp-Glu-Leu) at the carboxyl terminus. In this report, we examined whether other ER luminal proteins bearing the KDEL signal at their C-termini, such as BiP/GRP78 and endoplasmin/GRP94 are also exported from the ER. We prepared two kinds of affinity-purified polyclonal antibodies; one against a synthetic peptide with 12 amino acids which is identical to the carboxyl terminus of BiP and another against purified endoplasmin. Immunoblot analysis using these two antibodies showed that BiP and endoplasmin exist in both the plasma membrane and the microsomal fractions, similar to the intracellular distribution of PDI in rat exocrine pancreas. The ratios of the amount of the three proteins in the two fractions, however, were variable, suggesting that the KDEL-bearing proteins such as PDI, BiP, and endoplasmin are exported from the ER with different efficiencies. Postembedding protein A-immunogold electron microscopy revealed that endoplasmin was exported from the ER and secreted to the extracellular space. The secretion of PDI in rat pancreatic lobules was inhibited by Brefeldin A (BFA) and by guanidino acid esters (FOY-305), which are known to be the inhibitors of the intracellular transport. Taken together with the previous immunogold electron microscopic analyses by Akagi et al. (1988), it is strongly suggested that in rat exocrine pancreatic cells PDI and the other KDEL-bearing proteins found in the extracellular space were not artificially released by cell damage during incubation but were secreted via the normal secretory pathway.
 ...
PMID:Heavy chain binding protein (BiP/GRP78) and endoplasmin are exported from the endoplasmic reticulum in rat exocrine pancreatic cells, similar to protein disulfide-isomerase. 131 87

Most loss-of-function mutations of the glycoprotein hormone receptors have been found to be due to the misfolding of the receptor, resulting in its intracellular retention and, therefore, decreased cell surface expression. Chaperone proteins within the endoplasmic reticulum play an essential role in facilitating the folding of newly synthesized proteins and in recognizing and segregating misfolded proteins, thereby preventing their transit to the Golgi. The present study was conducted to begin to elucidate the role of chaperone proteins in the folding of the glycoprotein hormone receptors and misfolded mutants thereof. Toward this end, we examined the potential associations of calnexin, calreticulin, Grp94, BiP, ERp57, and protein disulfide-isomerase with each of the three glycoprotein hormone receptors. Calnexin, calreticulin, and protein disulfide-isomerase were found to associate with the immature forms of all three wild-type (wt) glycoprotein hormone receptors. As examples of misfolded glycoprotein hormone receptors, we studied two human LH receptor (hLHR) loss-of-function mutants that we show to be expressed predominantly as immature forms that are retained intracellularly. Significantly, the patterns of chaperone protein associations with the misfolded hLHR mutants differ from that observed with the wt hLHR. Furthermore, and unexpectedly, the chaperone protein associations were found to differ between the two misfolded hLHR mutants. Altogether, our studies show that although the same chaperone proteins are used by the three wt glycoprotein hormone receptors, different chaperone proteins associate with misfolded mutants thereof, and the specificity of interactions can vary between mutants, most likely reflecting the different stages of folding they achieve before being targeted for degradation.
 ...
PMID:Intracellularly located misfolded glycoprotein hormone receptors associate with different chaperone proteins than their cognate wild-type receptors. 1510 36

The interphotoreceptor matrix (IPM) is located between photoreceptors and pigment epithelium in the retina and is involved in fundamental functions of the visual cycle. These include visual pigment chromophore exchange, retinal adhesion, metabolite trafficking, and growth factor presentation. In general, IPM preparations are contaminated with intracellular proteins, as has also been described for other body fluids. This study aimed at identifying new components of the IPM by discriminating between truly secreted proteins and proteins that are part of the IPM for secondary reasons. "Soluble" porcine IPM was extracted from retina and pigment epithelium with PBS by two different procedures, followed by extraction with water alone that released "insoluble" IPM matrix sheets. Samples from all preparations were separated by 2-DE and a total of 140 protein spots were identified by MALDI-TOF and/or CapLC Q-TOF MS. Although identified proteins included several already known in the IPM, the majority had not been previously described in this structure. Gene ontology classifications allocated the identified proteins into nine different functional networks. The IPM preparations also included intracellular proteins from cells adjacent to the IPM, which may have resulted from cell disruption. This underlines the experimental difficulties of a biochemical analysis of the IPM as an intact compartment. We show here a strategy for predicting the probability of identified IPM proteins occurring in vivo by combined high-resolution protein separation methods with computational prediction methods. Thus, a set of potentially neuroprotective proteins could be extracted, including PEA-15, peroxiredoxin 5, alpha-B-crystallin, macrophage migration inhibitory factor, 78 kDa glucose-regulated protein (GRP78), protein disulfide-isomerase, and PEP-19, which have not been previously associated with the IPM. Furthermore, with immunohistochemical staining we could confirm the localization of GRP78 in the IPM on porcine eye sections, thus validating the proposed prediction method.
 ...
PMID:Proteomic analysis of the porcine interphotoreceptor matrix. 1612 31

Neurodegenerative diseases are often associated with misfolding and deposition of specific proteins in the nervous system. The prion protein, which is associated with transmissible spongiform encephalopathies (TSEs), is one of them. The normal function of the cellular form of the prion protein (PrP(C)) is mediated through specific signal transduction pathways and is linked to resistance to oxidative stress, neuronal outgrowth and cell survival. In TSEs, PrP(C) is converted into an abnormally folded isoform, called PrP(Sc), that may impair the normal function of the protein and/or generate toxic aggregates. To investigate these molecular events we performed a two-dimensional gel electrophoresis comparison of neuroblastoma N2a cells expressing different amounts of PrP(C) and eventually infected with the 22L prion strain. Mass spectrometry and peptide mass fingerprint analysis identified a series of proteins with modified expression. They included the chaperones Grp78/BiP, protein disulfide-isomerase A6, Grp75 and Hsp60 which had an opposite expression upon PrPC expression and PrP(Sc) production. The detection of these proteins was coherent with the idea that protein misfolding plays an important role in TSEs. Other proteins, such as calreticulin, tubulin, vimentin or the laminin receptor had their expression modified in infected cells, which was reminiscent of previous results. Altogether our data provide molecular information linking PrP expression and misfolding, which could be the basis of further therapeutic and pathophysiological research in this field.
 ...
PMID:Proteomic consequences of expression and pathological conversion of the prion protein in inducible neuroblastoma N2a cells. 2093 May 64

The study aimed to evaluate the proteomic changes in benign follicular adenoma versus malignant follicular variant of papillary thyroid carcinoma. Tumor and nontumor adjacent samples were analyzed by liquid nanochromatography mass spectrometry, and protein abundance was evaluated by label-free quantification. Western blotting and quantitative real-time polymerase chain reaction were used to validate and complement the mass spectrometry data. The results demonstrated deregulated expression of four endoplasmic reticulum chaperones (78 kDa glucose-regulated protein, endoplasmin, calnexin, protein disulfide-isomerase A4), glutathione peroxidase 3 and thyroglobulin, all of them involved in thyroid hormone synthesis pathway. The altered tissue abundance of endoplasmic reticulum chaperones in thyroid cancer was correlated with serum expression levels. The identified proteins significantly discriminate between adenoma and carcinoma in both thyroid tissue and corresponding sera. Data are available via ProteomeXchange with identifier PXD004322.
 ...
PMID:Endoplasmic Reticulum Chaperones Are Potential Active Factors in Thyroid Tumorigenesis. 2748 Jan 76

We attempted to identify the total proteome in sesame lipid droplets. Results from two-dimensional electrophoresis showed 139 protein spots in lipid droplet samples. Each spot was isolated, digested with trypsin, and applied to liquid chromatography-tandem mass spectrometry (Q-Tof Premier). As a result, 103 spots were identified. Although oleosin, caleosin, and steroleosin are known major components of the lipid droplet, many other proteins were also found in the lipid droplet. In addition to the three major proteins, TAG factor protein, glyceraldehyde-3-phosphate dehydrogenase, F1 ATPase, 70-kDa heat shock protein, seed maturation protein PM24, and 11S globulin precursor isoforms 3 and 4 were found in the lipid droplet. Three types of oleosins, 15-, 15.5-, and 17-kDa were present in the sesame lipid droplet, and the 15.5-kDa oleosin had high homology with oleosin from Coffea canephora. It has been shown by acid phosphatase treatment that oleosin proteins contain phosphate groups. Protein disulfide-isomerase 2 precursor, calreticulin-1, and BiP, which are known as marker proteins of the endoplasmic reticulum, were found as the components of the lipid droplet. Immunoconfocal microscopy was used to show that 11S globulin precursor isoform 3 and 4 were indeed localized in the lipid droplet. The presence of 11S globulin in the lipid droplets suggested a new mechanism for the lipid droplet formation.
 ...
PMID:Proteomic Analysis of Lipid Droplets in Sesamum indicum. 3247 80