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)

Glucose-regulated protein 58 (GRP58/ER-60/ERp57), best known as a chaperone in the endoplasmic reticulum lumen, was previously identified by us as one of several accessory proteins in the S100 cytosol fraction of human hepatoma Hep3B cells that was differentially coshifted by anti-Stat3 antibody in an antibody-subtracted differential protein display assay. In the present study, the association between GRP58 and Stat3 in different cytoplasmic compartments was evaluated using cross-immunoprecipitation and cell-fractionation techniques. In the S100 cytosol fraction, three different anti-GRP58 polyclonal antibodies (pAb) cross-immunoprecipitated Stat3 (but not Stat1), and, conversely, anti-Stat3 pAb cross-immunoprecipitated GRP58. Both cytosolic Stat3 and GRP58 eluted during Superose-6 gel-filtration chromatography in complexes of size 200-400 kDa (statosome I), and anti-Stat3 pAb cross-immunoprecipitated GRp58 from these FPLC elution fractions. Using differential sedimentation and density equilibrium flotation methods, Stat3 and GRP58 were observed to be coassociated with cytoplasmic membranes enriched for the plasma membrane marker 5' nucleotidase but not with those containing the endoplasmic reticulum marker BiP/GRP78. The Stat3 and GRP58-containing plasma membrane fraction also contained Stat1, Stat5b, and gp130. Stat activation by orthovanadate caused the accumulation of PY-Stat3 in the GRP58-containing plasma membrane fraction. However, this PY-Stat3 was DNA-binding deficient. Likewise, excess exogenous recombinant human GRP58 prepared using a baculovirus expression system preferentially inhibited Stat3 DNA-binding activity in the S100 cytosol, suggesting that GRP58 may sequester activated Stat3. The new data confirm the association between GRP58 and Stat3 in cytosolic 200-400-kDa statosome I complexes and show that both GRP58 and Stat family members coassociate in the plasma membrane compartment. We suggest that the chaperone GRP58 may regulate signaling by sequestering inactive and activated Stat3.
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PMID:Association of the chaperone glucose-regulated protein 58 (GRP58/ER-60/ERp57) with Stat3 in cytosol and plasma membrane complexes. 1206 Apr 94

S100 proteins are calcium-responsive signaling proteins that are overexpressed in cancer and inflammatory diseases. They act by forming complexes with target proteins to modify target protein function. Identifying S100 intracellular distribution, site of action, and protein targets are important goals. S100A7 (psoriasin) is an important member of this family that is markedly overexpressed in psoriatic keratinocytes; however, its role in disease progression is poorly understood. In this study, we express S100A7 in normal keratinocytes as a means to study S100A7 function. We show that S100A7 is present in the cytosol and in BiP/GRP78-positive (endoplasmic reticulum) tubular structures. When cells are challenged with elevated intracellular calcium, cytoplasmic S100A7 redistributes to alpha-actinin- and paxillin-positive peripheral structures that contact the substrate surface. Epidermal fatty acid binding protein is also overexpressed in psoriasis, and is a putative target of S100A7 in keratinocytes. To study this interaction, we coexpressed S100A7 and epidermal fatty acid binding protein. These studies indicate that S100A7 and epidermal fatty acid binding protein colocalize in the cytoplasm in untreated cultures, and localize in peripheral structures in response to calcium challenge. In addition, S100A7 expression appears to stabilize epidermal fatty acid binding protein level, and vice versa. Moreover, the proteins can be coprecipitated in the presence of bifunctional cross-linker, suggesting that they are part of a common complex. The colocalization with alpha-actinin and paxillin suggests that S100A7 and epidermal fatty acid binding protein colocalize in focal adhesion-like structures following calcium treatment.
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PMID:S100A7 (psoriasin) interacts with epidermal fatty acid binding protein and localizes in focal adhesion-like structures in cultured keratinocytes. 1283 73