The clinical trial is designed to evaluate the efficacy of bicyclol for patients with antineoplastic drug-induced liver injury and investigate factors effecting the therapeutic outcome.

开始日期2022-05-01

申办/合作机构

天津市肿瘤研究所

100 项与 HSP70 heat-shock proteins x PKC 相关的临床结果

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100 项与 HSP70 heat-shock proteins x PKC 相关的转化医学

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0 项与 HSP70 heat-shock proteins x PKC 相关的专利（医药）

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项与 HSP70 heat-shock proteins x PKC 相关的文献（医药）

2006-10-01·Journal of Biological Chemistry2区 · 生物学

Invariant Leu Preceding Turn Motif Phosphorylation Site Controls the Interaction of Protein Kinase C with Hsp70

2区 · 生物学

Article

作者: Alexandra C. Newton ; Tianyan Gao

Heat shock proteins play important roles in regulating signal transduction in cells by associating with, and stabilizing, diverse signaling molecules, including protein kinases. Previously, we have shown that heat shock protein Hsp70 associates with protein kinase C (PKC) via an interaction that is triggered by dephosphorylation at the turn phosphorylation motif. Here we have identified an invariant residue in the carboxyl terminus of PKC that mediates the binding to Hsp70. Specifically, we show that Hsp70 binds to Leu (Leu-640) immediately preceding the conserved turn motif autophosphorylation site (Thr-641) in PKC betaII. Co-immunoprecipitation experiments reveal that mutation of Leu-640 to Gly decreases the interaction of Hsp70 with PKC betaII. This weakened interaction between Hsp70 and the mutant PKCs results in accumulation of dephosphorylated PKC in the detergent-insoluble fraction of cells. In addition, the Hsp70-binding mutant is considerably more sensitive to down-regulation compared with WT PKC: disruption of Hsp70 binding leads to accelerated dephosphorylation and enhanced ubiquitination of mutant PKC upon phorbol ester treatment. Last, pulse-chase experiments demonstrate that Hsp70 preferentially binds the species of mature PKC that has become dephosphorylated compared with the newly synthesized protein that has yet to be phosphorylated. Thus, Hsp70 binds a hydrophobic residue preceding the turn motif, protecting PKC from down-regulation and sustaining the signaling lifetime of the kinase.

2004-10-01·Journal of Molecular and Cellular Cardiology2区 · 医学

Regulation of myocardial heat shock protein 70 gene expression following exercise

2区 · 医学

Article

作者: C.W. James Melling ; Earl G. Noble ; David B. Thorp

Post-exercise induction of myocardial heat shock protein (Hsp70) gene expression involves the activation of the heat shock transcription factor (HSF1). While the exact mechanisms governing the regulation of HSF1 are unclear, activation is believed to occur subsequent to hyperphosphorylation of specific serine residues. As two important serine kinases, protein kinase A (PKA) and protein kinase C (PKC), have been implicated in many phosphorylative events in myocardial cells, we examined the role of these kinases in the activation of Hsp70 gene expression following exercise. In this report, we show that prior administration of a PKA inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide ?2HCl (H-89; 0.36 mg/kg), significantly suppressed the elevation in Hsp70 mRNA (P < 0.05) and protein synthesis (P < 0.05) in male Sprague-Dawley rats following a single bout of exercise. In contrast, this post-exercise elevation in Hsp70 mRNA and protein synthesis was not suppressed following the administration of a PKC inhibitor chelerythrine chloride (CHEL; 5 mg/kg) (P < 0.05). Of note, inhibition of PKA did not alter the nuclear localization and binding affinity of HSF1 to the promotor region of the Hsp70 gene. These data indicate that PKA, and not PKC, plays a necessary role in the early exercise-induced regulation of Hsp70 gene expression, downstream of DNA-binding acquisition. However, the current study does not support previous observations regarding major changes in HSF1 phosphorylation and suggests that other PKA-related mechanisms mediate the activation of Hsp70 gene expression following exercise.

1996-09-01·European Journal of Biochemistry

Localization and Properties of Kinases in Clathrin‐Coated Vesicles from Zucchini Hypocotyls

Article

作者: Nicole Happel ; David G. Robinson ; Martin Drucker

Five major polypeptides of 70, 50, 47, 19 and 17 kDa and four minor polypeptides (100, 65, 45 and 39 kDa) become phosphorylated when clathrin‐coated vesicles (CCV) from zucchini hypocotyls are incubated in [γ32P]Mg‐ATP. After dissociation with 0.5 M Tris/HCl the CCV coat polypeptides were subjected to gel filtration in order to separate clathrin triskelions from β‐adaptin‐containing fractions. Only the latter bore kinase activities, with phosphorylated polypeptides of 39 kDa in addition to the 50, 19‐kDa and 17‐kDa polypeptides just mentioned. Heparin, an inhibitor of casein kinase II, permitted the phosphorylation of only the 19‐kDa and 17‐kDa polypeptides. Staurosporine, an inhibitor of protein kinase c‐like acitivities, prevented the phosporylation of the 70‐kDa polypeptide. When recombined with the triskelions the β‐adaptin fractions achieved the phosphorylation of the 45‐kDa and 70‐kDa polypeptides. Because of its heat stability and calcium‐binding properties we interpret the 45‐kDa polypeptide as being a clathrin light chain. Antibodies raised against the 70‐kDa group of heat‐shock proteins (Hsp70) recognize a 70‐kDa polypeptide in the β‐adaptin‐containing fractions. Because this polypeptide only phosphorylates in the presence of triskelions we consider it to be the uncoating ATPase, which is known to aggregate upon dissociation of the CCV coat. Our results therefore indicate that zucchini CCV contain a number of phosphorylable polypeptides equivalent to the β, μ and σ adaptins of bovine brain. Just as in bovine brain CCV a casein‐kinase‐II‐like activity is associated with the zucchini CCV 50/47‐kDa polypeptides, further pointing to their identity as plant μ2/μ1 adaptin equivalents.