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)

PiZ, a mutant human alpha 1-antitrypsin, is associated with liver and pulmonary disease and is characterized by defective secretion and accumulation of the protein in the endoplasmic reticulum. We tested the hypothesis that BiP (a protein that binds newly synthesized protein in the endoplasmic reticulum, prevents secretion of incorrectly folded protein, and solubilizes protein aggregates), could play a part in the retention of PiZ alpha 1-antitrypsin in the endoplasmic reticulum. Subcellular fractions from PiM (normal) and PiZ livers were prepared and analyzed by immunoblotting. No increase of BiP was detected in the PiZ liver. In addition, when total RNA from the same livers were analyzed by slot and Northern blot hybridization, no difference was found in the level of BiP mRNA between PiM and PiZ livers. Similar results were found in clones of CHO and MDCK cells transfected with PiM of PiZ alpha 1-antitrypsin cDNAs. These results indicate that BiP does not play a part in the retention of PiZ alpha 1-antitrypsin and suggest that PiZ protein is not misfolded.
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PMID:BiP expression is not increased by the accumulation of PiZ alpha 1-antitrypsin in the endoplasmic reticulum. 237 86

AtT-20 cells, which were derived from a murine pituitary tumor and produce ACTH, have until now been considered to originate from pituitary corticotrophs. Here we show that AtT-20 cells constitutively express several neuronal features. First, AtT-20 cells develop cytoplasmic processes whose fine structure is essentially identical to that of neurites and neuronal growth cones. These growth cones (i) are characterized by an extensive membranous reticulum which is derived from the endoplasmic reticulum (ER) since it contains immunoglobulin heavy chain binding protein, protein disulfide isomerase and glucose-6-phosphatase; (ii) are a major site of endocytosis; (iii) form cell-to-cell contacts resembling immature synapses. Second, AtT-20 cells, in contrast to pituitary corticotrophs, contain neurofilaments and express all three neurofilament polypeptides. They also contain the high molecular weight form of microtubule-associated protein 2 and tau protein. Third, AtT-20 cells express the neuron-specific phosphoprotein synapsin I which accumulates in the growth cones prior to contacts forming between growth cones and cells. Our results show that AtT-20 cells exhibit several properties of peptidergic neuronal cells and that the constitutive expression of a variety of these properties is compatible with continuous cell division.
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PMID:Morphological and biochemical evidence showing neuronal properties in AtT-20 cells and their growth cones. 250 49

The post-translational modifications of the G protein of vesicular stomatitis virus, described in the preceding paper, indicate that its transport is arrested by carbonylcyanide m-chlorophenylhydrazone (CCCP) in or near the trans-Golgi. Immunofluorescence microscopy of BHK-21 cells infected with vesicular stomatitis virus and treated with CCCP shows an accumulation of G protein in the Golgi area. In the same cells, the morphology of wheat germ agglutinin (WGA)-staining structures in the perinuclear region is aberrant. Using anti-BiP antibody, there is no obvious change in the structure of the endoplasmic reticulum. Electron microscopy reveals that the aberrant structures in the perinuclear region result from dilation of Golgi cisternae and accumulation of large vacuoles near the Golgi stack. The appearance of these aberrant structures is dose-dependent and they disappear after the protonophore is removed. The vast majority of the vacuoles accumulate on the trans side of the Golgi stack. A small fraction of them contain the marker enzyme thiamine pyrophosphatase (TPPase). By immunoelectron microscopy, most of the vacuoles contain G protein. We conclude that most of the Golgi-associated vacuoles are derived from a distal Golgi transport compartment, possibly the trans-Golgi reticulum, and that CCCP reversibly inhibits the transport of newly synthesized G protein through this distal compartment.
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PMID:The glycoprotein of VSV accumulates in a distal Golgi compartment in the presence of CCCP. 255 60

Immunoglobulin heavy chain binding protein (BiP) associates transiently with various proteins destined for the secretory pathway. To investigate the relationship between BiP and the 78K (K = 10(3) Mr) glucose-regulated protein (GRP78), we have determined a partial amino acid sequence of purified mouse BiP and isolated and sequenced a full-length cDNA clone encoding mouse GRP78. The 26 amino-terminal residues of the mature BiP protein are identical to a sequence of amino acids located near the start of the open reading frame encoding GRP78. A polyclonal antiserum raised against mouse GRP78 protein expressed in bacteria from the cloned GRP78 cDNA could immunoprecipitate complexes consisting of BiP and unfolded forms of immunoglobulin heavy chains. Furthermore, a monoclonal antibody raised against mouse BiP immunoprecipitated mouse GRP78 expressed in monkey CV-1 cells from an SV40-GRP78 recombinant vector. Finally, like the endogenous BiP of simian cells, mouse GRP78 associated with malfolded, non-glycosylated forms of influenza hemagglutinin (HA) when GRP78 and HA were co-expressed from SV40 vectors in CV-1 cells. These studies confirm that BiP is identical to GRP78. Comparison of the nucleic acid and deduced amino acid sequence of mouse GRP78 with those of other rodent and human GRP78s revealed an extremely high degree of sequence identity. BiP/GRP78 is closely related (approximately 60% identity) to the cytoplasmic 70K heat-shock proteins. Surprisingly, the carboxy-terminal 29 amino acids of BiP/GRP78, which are not conserved in HSP70 proteins, are almost identical in sequence to the steroidogenesis activator peptide found in the cytoplasm of rat Leydig tumor cells. Possible relationships between these polypeptides are discussed.
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PMID:Identification of immunoglobulin heavy chain binding protein as glucose-regulated protein 78 on the basis of amino acid sequence, immunological cross-reactivity, and functional activity. 255 88

The yeast KAR2 gene was isolated by complementation of a mutation that blocks nuclear fusion. The predicted KAR2 protein sequence is most homologous to mammalian BiP/GRP78 and has several structural features in common with it: a functional secretory signal sequence, a yeast endoplasmic reticulum retention signal (HDEL) at the carboxyl terminus, and the absence of potential N-linked glycosylation sites. Moreover KAR2 is regulated like BiP/GRP78: the level of mRNA is increased by drug treatments and mutations that cause accumulation of secretory precursors in the endoplasmic reticulum. However, unlike BiP/GRP78, KAR2 is also regulated by heat shock. Deletion of the KAR2 gene generated a recessive lethal mutation, showing that BiP/GRP78 function is required for cell viability.
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PMID:KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78 gene. 266 Oct 18

The endoplasmic reticulum (ER) of mammalian cells contains a 78 kd protein (BiP) that is believed to assist in the folding of secretory and transmembrane proteins. We have used a cDNA encoding mouse BiP to isolate the homologous gene from S. cerevisiae, which encodes a sequence of 682 amino acids, 431 of which are identical to mouse BiP. Like its mammalian counterpart, yeast BiP is encoded by an HSP70-like gene whose transcription is stimulated by the presence of unfolded polypeptides in the ER. The gene encoding yeast BiP is essential for cell growth and, unexpectedly, is identical to the recently cloned KAR2 gene. Expression of mammalian BiP in S. cerevisiae can complement a mutant allele of KAR2 that is temperature sensitive for growth and nonconditionally defective for karyogamy. These results suggest that deficiencies in BiP may cause generalized failure of protein folding in the ER, leading to pleiotropic effects on cellular metabolism.
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PMID:S. cerevisiae encodes an essential protein homologous in sequence and function to mammalian BiP. 266 Oct 19

Immunoglobulin heavy chain binding protein (BiP/GRP78) is a resident endoplasmic reticulum protein that binds tightly to a number of incompletely assembled or aberrant proteins. BiP also binds ATP and can be purified by ATP affinity chromatography. Here we show that an ATPase activity co-purifies with BiP prepared from canine pancreas. The BiP-associated ATPase has a high affinity for ATP but a low turnover number, suggesting a regulatory, rather than an enzymatic role. We also show that submicromolar levels of ATP or ADP decrease the rate of adsorption of [125I]BiP to nitrocellulose filters coated with protein or non-ionic detergents. In contrast, micromolar levels of AMP increase the rate of adsorption. Furthermore, ATP and ADP decrease the susceptibility of BiP to proteolytic degradation, whereas AMP was found to enhance degradation slightly. Adenine nucleotides may therefore induce or stabilize different conformations of BiP even when ATP hydrolysis does not occur.
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PMID:Interaction of heavy chain binding protein (BiP/GRP78) with adenine nucleotides. 267 May 54

Molecular chaperones are a ubiquitous family of proteins whose proposed role is to mediate the folding and assembly of other proteins into oligomeric structures. The essential function of molecular chaperones is to prevent the formation of incorrect structures which may result from the transient exposure of charged or hydrophobic surfaces normally involved in interactions between or within polypeptide chains. Such transient exposure may occur during the synthesis of polypeptides, the unfolding and refolding that occurs during their transport across membranes, the association of polypeptides made in one subcellular compartment with those made in another, changes in protein-protein interactions during the normal functioning of a complex, and recovery from stresses such as heat shock. Three classes of molecular chaperone are discussed: the nucleoplasmins, the BiP group, and the chaperonins.
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PMID:The molecular chaperone concept. 269 89

We have characterized the association between the binding protein, BiP (also known as GRP 78), and misfolded forms of the influenza virus hemagglutinin precursor, HA0. BiP is a heat-shock-related protein that binds to unassembled immunoglobulin heavy chain and to a variety of misfolded proteins in the lumen of the ER. A small fraction (5-10%) of newly synthesized HA0 in CV-1 cells was found to be misfolded and retained in the ER. When glycosylation was blocked with tunicamycin, all of the HA0 produced was similarly misfolded. The misfolded HA0 was retained as relatively small (9-25-S) complexes associated with BiP. In these complexes the top domains of HA0 were correctly folded judging by their reactivity with monoclonal antibodies, but the polypeptides were cross-linked via anomalous interchain disulfides. The association with BiP was non-covalent and easily broken by warming to 37 degrees C or by adding ATP to the lysate. Pulse-chase experiments showed that HA0's self-association into complexes occurred immediately after synthesis and was followed rapidly by BiP association. The misfolded, BiP-associated HA0 was not transported to the plasma membrane but persisted as complexes in the ER for a long period of time before degradation (t1/2 = 6 h). The results suggested that BiP may be part of a quality control system in the ER and that one of its functions is to detect and retain misfolded proteins.
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PMID:Interactions of misfolded influenza virus hemagglutinin with binding protein (BiP). 273 90

In guinea pig exocrine pancreatic cells intracisternal granules (ICGs) occur at a low frequency within the lumen of the RER. By starving and refeeding guinea pigs or injecting them in CoCl2 solution, the number of these granules is greatly increased. We show here that ICGs contain the complete set of secreted pancreatic digestive enzymes and proenzymes. Two other soluble proteins in the lumen of the RER, GRP 78/BiP and protein disulphide isomerase (PDI), are specifically excluded from ICGs. The formation of ICGs, which occurs without acidification of the RER cisternae, is therefore a sorting event involving the cocondensation of a complete set of secretory enzymes and proenzymes, which for brevity we refer to collectively as the zymogens. With the exception of approximately 50% of the RNase, the zymogens in ICGs are covalently cross-linked by intermolecular disulphide bonds. The synthesis of all three resident ER cisternal proteins--PDI, GRP 78/BiP, and GRP 94--with the carboxy-terminal sequence KDEL, is induced in response to the accumulation of massive amounts of misfolded secretory protein in the ICGs in the lumen of the RER. After injection of rats with large doses of parachlorophenylalanine-methylester, crystals form in the lumen of the RER. We show that these crystals appear to be a lattice of amylase with the other zymogens incorporated between the layers. Both GRP 78/BiP and PDI are excluded from these crystals. The formation of these amylase crystals within the RER and the inclusion of other zymogens is, therefore, also a sorting event. These data establish that in exocrine pancreatic cells zymogens can cocondense in the RER into either amorphous aggregates or crystals that exclude other soluble RER proteins. This demonstrates that cocondensation is a mechanism capable of sorting zymogens within the secretory pathway.
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PMID:Condensation-sorting events in the rough endoplasmic reticulum of exocrine pancreatic cells. 274 55


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