Disease relevance of Ptpra

• These data thus show that the t-PA clearance receptor identified on MH1C1 hepatoma cells is LRP/alpha 2MR [1].
• Cellular intoxification by exotoxin A of Pseudomonas aeruginosa (PEA) begins when PEA binds to its cellular receptor, the low-density lipoprotein receptor-related protein (LRP) [2].
• Down-regulation of hepatic LDL receptor-related protein (LRP) in chronic renal failure [3].
• Using a [(3)H]leucine incorporation assay to measure inhibition of protein synthesis, we have demonstrated that HS-P macrophages are highly sensitive to PEA and that PEA toxicity is decreased by the LRP antagonist receptor-associated protein [2].
• Statin administration for 2 wk resulted in significant improvements of plasma lipid profile, proteinuria, and hypoalbuminemia as well as hepatic LRP mRNA and protein abundance [4].

Psychiatry related information on Ptpra

• Thus, constitutive endocytosis of anionic liposomes by LRP utilizes only one component, in contrast to the more involved heparan sulfate proteoglycan-LRP pathway implicated in the pathogenesis of Alzheimer's disease [5].

High impact information on Ptpra

• These data suggest a high rate of synthesis of LRP that appeared to be unaffected by treatment of rats with estradiol [6].
• The high concentration of LRP in hepatic endosomal membranes greatly facilitated demonstration of Ca-dependent binding of apolipoprotein E- and B-containing lipoproteins in ligand blots [6].
• It is insensitive to blockade of action potentials by tetrodotoxin or inhibition of binding of apoE by heparinase, by the LRP ligand lactoferrin and by low density lipoprotein [7].
• A function of RAP may be to prevent premature interaction of LPL with binding partners in the secretory pathway, namely LRP and heparan sulfate proteoglycan [8].
• We conclude that HL is partially and LPL almost exclusively taken up into rat hepatocytes after binding to the endocytic receptor LRP [9].

Chemical compound and disease context of Ptpra

• Tissue-type plasminogen activator (t-PA), a plasma serine protease that binds specifically and with high affinity to LRP on hepatoma cells, also binds to endothelial cells and vascular smooth muscle cells [10].

Biological context of Ptpra

• By Northern analysis, a ubiquitous pattern of LRP gene expression in rat tissues was demonstrated [11].
• Instead, LRP was redistributed to the cell surface and remained localized primarily in coated pits, as determined by surface protein biotinylation, affinity labeling, and immunoelectron microscopy studies [12].
• To investigate the pathophysiological role of LRP in the central nervous system, we examined the effects of activated alpha(2)-macroglobulin (alpha2M*), a ligand of LRP, on intracellular calcium signaling in cultured rat hippocampal neurons [13].
• CONCLUSION: CRF results in down-regulation of hepatic LRP [3].
• This suggests that the apoE content of chylomicron remnants is sufficient for its recognition by LDL receptors but additional apoE is required for its uptake by the LRP and that there is an up-regulation of a non-LDL receptor family mechanism in apoE deficiency [14].

Anatomical context of Ptpra

• cDNA cloning of rat LRP, a receptor like protein tyrosine phosphatase, and evidence for its gene regulation in cultured rat mesangial cells [11].
• Low density lipoprotein receptor-related protein (LRP) is a multifunctional receptor, expressed by vascular smooth muscle cells (VSMCs) in normal arteries and in atherosclerotic lesions [12].
• There is increasing evidence that the low-density lipoprotein receptor-related protein (LRP) can function as a signaling link in the central nervous system [13].
• Mouse embryonic fibroblasts, which express LRP, mediate the cellular internalization leading to degradation of these SECs, while mouse fibroblasts genetically deficient in LRP showed no capacity to internalize and degrade these complexes [15].
• In the current studies, we provide evidence that LRP is present on the surface of primary adipocytes isolated from rat epididymal fat pads [16].

Associations of Ptpra with chemical compounds

• Native alpha2M, which is not a ligand for LRP, did not affect signals to NMDA [13].
• SECs were also degraded by HepG2 cells, and this process was inhibited by LRP antibodies, RAP, and chloroquine [15].
• The increase in cell-surface LRP was partially explained by a 50% decrease in receptor endocytosis rate; however, at 37 degrees C, PDGF-BB- and EGF-treated VSMCs still bound/internalized increased amounts of activated alpha2M and subsequently released increased amounts of trichloroacetic acid-soluble radioactivity [12].
• In rats fed with cholesterol there was a significant increase in these particles in plasma (1.21 +/- 0.4 versus 5.71 +/- 0.4 mg/dl), whereas the expression of LRP was unaltered [17].
• We have examined the effect of lipopolysaccharide (LPS) on LRP expression and PEA sensitivity in the macrophage-like cell line HS-P [2].

Regulatory relationships of Ptpra

• In cultured rat mesangial cells, LRP mRNA was detected and the mRNA level was suppressed by either interleukin-1 or interleukin-6 treatment [11].

Other interactions of Ptpra

• To understand the significance of PTPases in physiological and pathophysiological processes in the kidney, we isolated three cDNA segments encoding PTPases (LAR, LRP and a novel PTPase) from rat kidney by polymerase chain reaction (PCR) [11].
• Six down-regulated clones were microtubule-associated protein 1B, protein tyrosine phosphatase alpha, Kv1.2 channel, myelin protein SR13, medium-sized neurofilament protein, and one novel gene [18].

Analytical, diagnostic and therapeutic context of Ptpra

• Using PCR product as a probe, we isolated a full-length cDNA of rat LRP [11].
• Another recently identified membrane receptor, low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR), was also detected on MH1C1 hepatoma cells by using immunoprecipitation with anti-LRP/alpha 2MR antibody [1].
• When analyzed by SDS/PAGE, we found the t-PA receptor identified on MH1C1 cells comigrated with the large subunit of LRP/alpha 2MR [1].
• Here using in situ hybridization and quantitative RNase protection assays, we show that LRP is also expressed throughout the brain [19].
• Northern and Western blot analyses demonstrated that neither PDGF-BB nor EGF increase LRP mRNA or protein levels [12].

References