Disease relevance of Mvp

• Interaction of Src and MVP was also observed in 253J stomach cancer cells [1].
• To gain insight into the mechanisms for vault assembly, we have expressed rat MVP in the Sf9 insect cell line using a baculovirus vector [2].
• METHODS: By using real-time polymerase chain reaction (PCR) analysis and immunocytochemistry, we quantified MVP mRNA and protein from the dentate gyrus (DG) and parahippocampal cortex (PHC) taken from EEG-monitored rats at 1 week after electrically induced status epilepticus (SE) and at 5-9 months after SE, when rats exhibit spontaneous seizures [3].
• PURPOSE: Because drug transporters might play a role in the development of multidrug resistance (MDR), we investigated the expression of a vesicular drug transporter, the major vault protein (MVP), in a rat model for temporal lobe epilepsy [3].

High impact information on Mvp

• MVP protein increased within 1 day after SE in reactive microglial cells within most limbic regions; the hippocampus showed the highest expression at 1 week after SE [3].
• Inhibitors of casein kinase II attenuate the phosphorylation of MVP [4].
• In contrast to CHO cells, addition of recombinant casein kinase II enhances the phosphorylation of MVP in PC12 cells [4].
• The susceptibility to protein kinases differs substantially from those observed in MVP derived from electric organ [4].
• Immuno-affinity purified vaults containing recombinant tagged MVP expressed in CHO cells reveal no autophosphorylation, suggesting that protein kinase activity is not an intrinsic property of vaults [4].

Biological context of Mvp

• We found MVP as a Src-SH2 binding protein in human stomach tissue [1].
• Although the first direct evidence for a causal relationship between LRP/MVP expression and drug resistance has been obtained, many functional aspects of vaults in normal physiology and in MDR still need to be clarified [5].
• Comparative analysis of the effects of intravesical instillation of drugs on urodynamic parameters (MVP, maximum intravesical pressure; RR, residual rate; BC, bladder capacity) was performed using an experimental model in unanesthetized rats [6].

Anatomical context of Mvp

• Major vault protein is a substrate of endogenous protein kinases in CHO and PC12 cells [4].
• Here we show that MVP from two mammalian cell lines (CHO and PC12 cell) becomes highly phosphorylated by endogenous protein kinases in cell-free systems [4].

Associations of Mvp with chemical compounds

• We have previously shown that MVP derived from electric ray electric organ becomes phosphorylated by protein kinase C in vitro and by tyrosine kinase in vivo [4].
• Phosphorylation of MVP depends on the presence of Mg2+ and can be inhibited by the chelating agent EDTA [4].
• Isoproterenol suppressed MVP with an increase of RR and BC in a dose-dependent manner at a relatively high concentration [6].
• Atropine showed, however, no suppression of MVP in spite of a significant change of RR and BC [6].
• Of the anticholinergics, propantheline and oxybutynin showed a remarkable suppression of MVP accompanied with a consistent increase of RR and BC in a dose-dependent manner [6].

Analytical, diagnostic and therapeutic context of Mvp

• Southern blot analysis indicates that the rat MVP is a single-copy gene [7].
• Our results show that the expression of the rat MVP alone can direct the formation of particles that have biochemical characteristics similar to endogenous rat vaults and display the distinct vault-like morphology when negatively stained and examined by electron microscopy [2].

References