Expression of the glucose-regulated proteins (GRP94 and GRP78) in differentiated and undifferentiated mouse embryonic cells and the use of the GRP78 promoter as an expression system in embryonic cells

Kim, Kyu Seong; Kim, Yong Kyu; Lee, Amy

doi:10.1111/j.1432-0436.1990.tb00756.x

Cited by 39 publications

(24 citation statements)

References 38 publications

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“…GRP94 has been shown to be expressed in oocytes during early embryonic development and at later stages of organogenesis and is lowered to a basal level in adults (61)(62)(63). During tumorigenesis and metastasis, additional proteins are synthesized, which appear to correlate with increased expression of GRP94.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport

Ghosh

Shinogle

Galeva

et al. 2016

Journal of Biological Chemistry

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Heat shock protein 90 (HSP90) is a molecular chaperone that is up-regulated in cancer and is required for the folding of numerous signaling proteins. Consequently, HSP90 represents an ideal target for the development of new anti-cancer agents. The human HSP90 isoform, glucose-regulated protein 94 (GRP94), resides in the endoplasmic reticulum and regulates secretory pathways, integrins, and Toll-like receptors, which contribute to regulating immunity and metastasis. However, the cellular function of GRP94 remains underinvestigated. We report that GRP94 knockdown cells are defective in intracellular transport and, consequently, negatively impact the trafficking of F-actin toward the cellular cortex, integrin ␣2 and integrin ␣L toward the cell membrane and filopodia, and secretory vesicles containing the HSP90␣-AHA1-survivin complex toward the leading edge. As a result, GRP94 knockdown cells form a multipolar spindle instead of bipolar morphology and consequently manifest a defect in cell migration and adhesion.Cell migration is the process by which cells move during developmental morphogenesis, tissue repair and regeneration, and cancer metastasis. During metastasis, cancer cells polarize in response to chemokines or environmental cues originating from the extracellular matrix (ECM). 2 With the assistance of microtubules, the microtubule-organizing center and the Golgi apparatus orient toward the direction of migration to aid vesicular transport toward the leading edge (1, 2). At the leading edge of the polarized cell, actin polymerization occurs rapidly to form lamellipodia, from which slender cytoplasmic projections called filopodia develop (3-5). These filopodia play roles in sensing, migration, cell-cell interactions, and adhesion (6). Adhesion of filopodia and lamellipodia to the ECM occurs through integrin receptors. Integrin receptors are a large superfamily of heterodimeric receptors that bind ECM ligands or cognate ligands on adjacent cells. The macromolecular assembly through which mechanical force and regulatory signals are transmitted between the ECM and a neighboring cell is described as a focal adhesion, which is composed of integrins, adapter proteins, and signaling molecules (7). The focal adhesion complex undergoes endo-exocytic cycles, and disruption of the endosomal transport or exocytic fusion of recycling vesicles affects cell polarity and migration (8, 9).The endoplasmic reticulum (ER) is the manufacturing site of newly synthesized proteins that are folded and targeted to their destination. The ER works continuously with the outer layer of the nuclear envelope but separate from the Golgi apparatus. Protein transport from the ER to Golgi occurs through coatomer I-and II-coated vesicles, with final transport to the plasma membrane occurring via endosomes. Cell migration requires the transport of proteins to the leading edge to establish cell polarity, filopodia and lamellipodia formation, adhesion, signaling, and translocation. In addition, several secretory proteins are required at the leading...

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Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport

Ghosh

Shinogle

Galeva

et al. 2016

Journal of Biological Chemistry

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“…BiP levels are tightly controlled and are elevated upon physiological (e.g., cell differentiation increasing the ER load with cargo proteins) or pathological (accumulation of misfolded proteins) stress responses. During embryogenesis, BiP expression remains below detection limit to the morula stage, but becomes abundant at the blastocyst stage in E3.5 embryos (196). It is therefore not surprising that the BiP Ϫ/Ϫ mice cannot survive beyond this stage, and the cells when cultured in vitro cannot proliferate and rapidly degenerate (235).…”

Section: The Classical Chaperonesmentioning

confidence: 99%

In and Out of the ER: Protein Folding, Quality Control, Degradation, and Related Human Diseases

Hebert¹,

Molinari²

2007

Physiological Reviews

578

559

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A substantial fraction of eukaryotic gene products are synthesized by ribosomes attached at the cytosolic face of the endoplasmic reticulum (ER) membrane. These polypeptides enter cotranslationally in the ER lumen, which contains resident molecular chaperones and folding factors that assist their maturation. Native proteins are released from the ER lumen and are transported through the secretory pathway to their final intra- or extracellular destination. Folding-defective polypeptides are exported across the ER membrane into the cytosol and destroyed. Cellular and organismal homeostasis relies on a balanced activity of the ER folding, quality control, and degradation machineries as shown by the dozens of human diseases related to defective maturation or disposal of individual polypeptides generated in the ER.

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“…In addition, Grp94 also bind to peptides in vivo and in vitro (24 -26). Mouse knockouts of Grp94 are embryonically lethal at mesoderm formation, suggesting an important role for this protein in early development (27). In Leishmania, parasite virulence seems to depend on Grp94 (28).…”

Section: The Hsp90mentioning

confidence: 99%

The ATPase Cycle of the Endoplasmic Chaperone Grp94

Frey

Leskovar

Reinstein

et al. 2007

Journal of Biological Chemistry

106

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Grp94, the Hsp90 paralog of the endoplasmic reticulum, plays a crucial role in protein secretion. Like cytoplasmic Hsp90, Grp94 is regulated by nucleotide binding to its N-terminal domain. However, the question of whether Grp94 hydrolyzes ATP was controversial. This sets Grp94 apart from other members of the Hsp90 family where a slow but specific turnover of ATP has been unambiguously established. In this study we aimed at analyzing the nucleotide binding properties and the potential ATPase activity of Grp94. We show here that Grp94 has an ATPase activity comparable with that of yeast Hsp90 with a k cat of 0.36 min

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Expression of the glucose-regulated proteins (GRP94 and GRP78) in differentiated and undifferentiated mouse embryonic cells and the use of the GRP78 promoter as an expression system in embryonic cells

Cited by 39 publications

References 38 publications

Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport

Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport

In and Out of the ER: Protein Folding, Quality Control, Degradation, and Related Human Diseases

The ATPase Cycle of the Endoplasmic Chaperone Grp94

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