Disease relevance of Mvp

• Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics [1].
• Furthermore, the activities of the ABC-transporters P-glycoprotein, multidrug resistance-associated protein and breast cancer resistance protein were unaltered on MVP deletion in these cells [1].
• Functionality of the receptor was evaluated by exposing cells to Pseudomonas exotoxin A. alpha-2 MR/LRP is responsible for Pseudomonas exotoxin A internalization, and only the parental cells exhibited toxin-mediated cytotoxicity [2].
• The differential recognition of serpin-protease complexes by fibroblasts and hepatoma cells, however, indicates that LRP, gp330, and the serpin-enzyme complex receptor are distinct proteins [3].
• We and others have used the term MVP dysautonomia for a particular subset of hyperadrenergic dysautonomia patients [4].

Psychiatry related information on Mvp

• The low-density lipoprotein receptor-related protein (LRP) has recently been implicated in numerous intracellular signaling functions, as well as in Alzheimer's disease pathogenesis [5].

High impact information on Mvp

• The low density lipoprotein receptor-related protein (LRP) is a large multifunctional clearance receptor that has been implicated in the hepatic uptake of chylomicron remnants and in the removal of protease-inhibitor complexes from the circulation and from the extracellular space [6].
• Whereas LRP activity was normal, livers from treated mice incorporated significantly less sulfate into heparan sulfate proteoglycans (HSPG) than did controls [7].
• Our results clearly demonstrate that two independent receptor systems, LRP and the mannose receptor, are involved in the hepatic clearance of t-PA [8].
• Two distinct clearance mechanisms, which are mediated by the low density lipoprotein receptor-related protein (LRP) on liver parenchymal cells and by the mannose receptor on liver endothelial cells, have been described [8].
• Using deletion constructs, the critical region in LRP that modulates APP processing was mapped to a seven peptide domain around the second NPXY domain (residues 4504-4510) [5].

Chemical compound and disease context of Mvp

• Abnormal guanine nucleotide regulatory protein in MVP dysautonomia: evidence from reconstitution of Gs [4].

Biological context of Mvp

• The regulation of MVP tyrosyl phosphorylation by SHP-2 may play an important role in cell survival signaling [9].
• Analysis of nucleo-cytoplasmic transport using a fluorescent substrate containing a classical NLS and NES expressed in MVP+/+ and MVP-/- mouse embryonic fibroblasts indicated no differences in nuclear import/export kinetics, suggesting no role for vaults in these processes [10].
• We have isolated the murine MVP cDNA and compared the amino acid sequence with MVP from other species [11].
• We also found that the genomic structure of the murine MVP gene closely resembles the organization of the human MVP gene, both consisting of 15 exons of which most have exactly the same size [11].
• These results suggest that up-regulation of MVP in multi-drug resistance (MDR) may involve chromatin remodeling [12].

Anatomical context of Mvp

• Neither the MVP(-/-) embryonic stem cells nor the MVP(-/-) bone marrow cells showed an increased sensitivity to any of the drugs examined, as compared with wild-type cells [1].
• There was no significant activation of either the MVP or VPARP promoters in drug-resistant cell lines in comparison to their parental, drug-sensitive counterparts [12].
• We now demonstrate that binding of lactoferrin, Pseudomonas exotoxin A, and lipoprotein lipase to LRP on macrophages results in increased [Ca2+]i and inositol 1,4,5-triphosphate [13].
• To investigate the intracellular pathway of the LRP signaling involved in neurite outgrowth, we tested the effects of alpha2M* on the phosphorylation of the mitogen-activated protein (MAP) extracellular signal-regulated kinases 1 and 2 (ERK1/2) [14].
• Cs complexes do not stimulate neutrophil or monocytic chemotaxis but are removed by LRP, further underscoring its role as a serpin-enzyme complex clearance receptor [15].

Associations of Mvp with chemical compounds

• In addition, MVP wild-type and deficient mice were treated with the anthracycline doxorubicin [1].
• Furthermore, treatment with trichostatin A (TSA), a more specific inhibitor of HDAC, caused an increase in MVP protein, mRNA, and promoter activity [12].
• The endocytic receptor protein LRP also mediates neuronal calcium signaling via N-methyl-D-aspartate receptors [16].
• SECs were also degraded by HepG2 cells, and this process was inhibited by LRP antibodies, RAP, and chloroquine [17].
• These studies are the first to identify a putative binding site in a serine protease inhibitor that is required for LRP-mediated internalization [18].

Other interactions of Mvp

• To confirm a direct relation between vaults and multidrug resistance, and to investigate other possible functions of vaults, we have generated a major vault protein (MVP/lung resistance-related protein) knockout mouse model [1].

Analytical, diagnostic and therapeutic context of Mvp

• Immunoprecipitation experiments corroborated these results showing co-precipitation of MVP and beta-tubulin [10].
• Cryoelectron microscopy imaging of recombinant and tissue derived vaults: localization of the MVP N termini and VPARP [19].
• To inhibit LRP, the 39-kD protein, which is a potent inhibitor of LRP activity, was overexpressed in the liver of mice using an adenoviral gene transfer technique [8].
• The cell culture and in vivo experiments revealed that HSPGs are also involved in another, LRP-independent pathway of fVIII catabolism [20].
• By immunoblotting of CNBr-digested LRP it is shown that Fab A8 binds to a fragment that harbors the second cluster of cysteine-rich complement-type repeats flanked by epidermal growth factor repeats [21].

References