Expression of wild-type and mutant forms of influenza hemagglutinin: The role of folding in intracellular transport

Gething, Mary‐Jane; McCammon, Karen; Sambrook, Joe

doi:10.1016/0092-8674(86)90076-0

Cited by 840 publications

(623 citation statements)

References 41 publications

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“…Induction of transcription and translation of the BiP gene occurs when an improperly folded mutant of the influenza virus hemagglutinin is expressed in CV-1 cells [17] and accumulates in the ER [8]. Although PiZ alAT accumulates in large amounts in the ER of hepatocytes, a similar increase in the expression of the BiP gene could not be demonstrated here.…”

Section: Resultsmentioning

confidence: 49%

BiP expression is not increased by the accumulation of PiZ α₁‐antitrypsin in the endoplasmic reticulum

et al. 1990

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PiZ, a mutant human a,-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 a,-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 a,-antitrypsin cDNAs. These results indicate that BiP does not play a part in the retention of PiZ a,-antitrypsin and suggest that PiZ protein is not misfolded.

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Section: Resultsmentioning

confidence: 49%

BiP expression is not increased by the accumulation of PiZ α₁‐antitrypsin in the endoplasmic reticulum

et al. 1990

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“…In a related study it was demonstrated that preexisting Ig heavy chains complexed with GRP78-BiP can be displaced by the in vivo addition of Ig light chains, resulting in the assembly and secretion of Ig (Hendershot, 1990). In addition to its role in assembly of HN and G, GRP78-BiP has been observed to be more stably associated with altered forms of HN or G that are malfolded (Machamer et al, 1990;, as has also been found with malfolded forms of several other proteins, including the influenza virus hemagglutinin (Gething et al, 1986;.…”

Section: Introductionmentioning

confidence: 86%

“…However, these observations should not be necessarily interpreted to suggest that GRP78-BiP is absent from the process of folding of mutant HC because either deletion mutant may continue to contain the other available binding sites. Newly synthesized molecules in the ER must properly fold and assemble before transport to the Golgi apparatus (Gething et al, 1986;Copeland et al, 1986). Although there is mounting evidence that molecular chaperones such as GRP78-BiP are involved in the folding of polypeptides, it must be stressed that additional factors may be essential in promoting folding of proteins in the secretory pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Considerable evidence has accumulated indicating that for a protein to be transported out of the ER it must be properly folded and oligomerized (Gething et al, 1986;reviewed in . As GRP78-BiP has often been found associated in a semistable manner with incompletely assembled or malfolded proteins, it has been proposed that it may play a role in retention of proteins in the ER (Bole et al, 1986;Dorner et al, 1987;.…”

Section: Intracellular Localization Of Hn Mutant Proteinsmentioning

confidence: 99%

“…Although the precise function of GRP78-BiP has not yet been defined, more recently it has been suggested to have a general role in the folding and assembly of proteins in the ER (Gething et al, 1986;Munro and Pelham, 1986;Pelham, 1986), to mark aberrantly folded proteins destined for degradation (Gething et al, 1986;Dorner et al, 1987;Lodish, 1988;, or to aid in solubilizing aggregated proteins during times of stress (Munro and Pelham, 1986). Studies using viral membrane glycoproteins as models have implicated a role for GRP78-BiP in the general folding and assembly of proteins in the exocytic pathway.…”

Section: Introductionmentioning

confidence: 99%

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Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene.

Watowich

Lamb

1992

MBoC

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The endoplasmic reticulum (ER)-localized chaperone protein, GRP78-BiP, is involved in the folding and oligomerization of secreted and membrane proteins, including the simian virus 5 hemagglutinin-neuraminidase (HN) glycoprotein. To understand this interaction better, we have constructed a series of HN mutants in which specific portions of the extracytoplasmic domain have been deleted. Analysis of these mutant polypeptides expressed in CV-1 cells have indicated that GRP78-BiP binds to selective sequences in HN and that there exists more than a single site of interaction. Mutant polypeptides have been characterized that are competent and incompetent for association with GRP78-BiP. These mutants have been used to show that the induction of GRP78-BiP synthesis due to the presence of nonnative protein molecules in the ER is dependent on GRP78-BiP complex formation with its substrates. These studies have implications for the function of the GRP78-BiP protein and the mechanism by which the gene is regulated. INTRODUCTIONThe 78-kDa glucose-regulated/Ig heavy-chain binding protein (GRP78-BiP) is a member of the highly con-

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Down-regulation of epidermal growth factor receptor-signaling pathway by binding of GRP78/BiP to the receptor under glucose-starved stress conditions

et al. 1998

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GRP78/BiP, a molecular chaperone in the endoplasmic reticulum, is induced under such adverse conditions for cell survival as glucose starvation. Induction of GRP78 has been shown to coincide with G1 cell cycle arrest, which is an important cellular defense system. In this study, we investigated involvement of GRP78 in the mechanism of growth arrest by using human epidermoid carcinoma A431 cells. Under a chemical stress condition with 2-deoxyglucose, GRP78 was induced 3-4-fold. In the stressed cells, an underglycosylated form of epidermal growth factor receptor (EGFR) was produced and the mature form was decreased. We found that the molecular chaperone GRP78 in the endoplasmic reticulum formed a stable complex with the underglycosylated EGFR but did not with the mature form. This complex formation occurred specifically under the stress conditions, and the complex was dissociated upon removal of the stress. Treatment of the GRP78-underglycosylated EGFR complex with ATP resulted in a release of the underglycosylated EGFR from GRP78, indicating that the complex could be formed through the chaperone function of GRP78. In accordance with the complex formation with endoplasmic reticulum-resident GRP78, the underglycosylated EGFR could not be translocated to the cell surface. As a result, EGF could not induce expression of cyclin D3, a G1 cyclin, in the stressed cells, whereas it did in non-stressed cells. These results indicated that, in the stressed cells, GRP78 participated in down-regulation of EGF-signaling pathway by forming a stable complex with EGFR and inhibiting EGFR translocation to the cell surface.

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Expression of wild-type and mutant forms of influenza hemagglutinin: The role of folding in intracellular transport

Cited by 840 publications

References 41 publications

BiP expression is not increased by the accumulation of PiZ α₁‐antitrypsin in the endoplasmic reticulum

BiP expression is not increased by the accumulation of PiZ α₁‐antitrypsin in the endoplasmic reticulum

Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene.

Down-regulation of epidermal growth factor receptor-signaling pathway by binding of GRP78/BiP to the receptor under glucose-starved stress conditions

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Expression of wild-type and mutant forms of influenza hemagglutinin: The role of folding in intracellular transport

Cited by 840 publications

References 41 publications

BiP expression is not increased by the accumulation of PiZ α1‐antitrypsin in the endoplasmic reticulum

BiP expression is not increased by the accumulation of PiZ α1‐antitrypsin in the endoplasmic reticulum

Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene.

Down-regulation of epidermal growth factor receptor-signaling pathway by binding of GRP78/BiP to the receptor under glucose-starved stress conditions

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BiP expression is not increased by the accumulation of PiZ α₁‐antitrypsin in the endoplasmic reticulum

BiP expression is not increased by the accumulation of PiZ α₁‐antitrypsin in the endoplasmic reticulum