Disease relevance of PTPRO

• Previous study in our laboratory demonstrated suppression of the gene for protein tyrosine phosphatase receptor-type O (PTPRO) in primary and established rat hepatomas [1].
• Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer [1].
• Glomeruli from human renal biopsies with crescentic nephritis showed focal to diffuse disappearance of GLEPP1 protein [2].
• Synaptopodin expression correlated with the severity of proteinuria and with GLEPP1 expression [3].
• GLEPP1 distribution pattern and absence from glomeruli of individuals with nephrotic syndrome may, therefore, represent a useful phenotypic marker [4].

High impact information on PTPRO

• Perfusion of rat kidneys with the polycation protamine sulfate caused glomerular epithelial alterations resembling those observed in human and experimental nephrotic states [5].
• The GLEPP1 gene (PTPRO:) was disrupted at an exon coding for the NH(2)-terminal region by gene targeting in embryonic stem cells [6].
• Furthermore, transfection of the human MMP-9 cDNA into rat glomerular epithelial cells yielded the 98-kD product [7].
• Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy [7].
• In this study a 98-kD neutral proteinase secreted by cultured rat visceral glomerular epithelial cells was shown to be a calcium, zinc-dependent enzyme secreted in latent form [7].

Chemical compound and disease context of PTPRO

• Glomerular epithelial cell changes after ischemia or dehydration. Possible role of angiotensin II [8].
• This CS alteration coincided with changes in glomerular epithelial cell morphologic characteristics (increased cytoplasmic organelles and rough endoplasmic reticulum) and preceded the detection of foot process broadening (at 24 hours) and increased urinary albuminuria (suggested at 12-24 hours, statistically significant at 36-48 hours) [9].
• Glomerular epithelial cell arachidonate metabolism in Shiga toxin hemolytic uremic syndrome [10].
• The degree of fusion of glomerular epithelial cell foot processes was quantitated by determining the mean number of inter-process slip pores along 10 mum of basement membrane of peripheral capillary walls in 45 children with steroid-responsive nephrotic syndrome and minimal lesion glomerulopathy [11].
• 3. The target cell toxicity in vivo of adriamycin, 2-bromoethanamine and hexachlorobutadiene N-acetyl cysteine conjugate is selectively maintained towards glomerular epithelial, medullary interstitial and proximal tubular cells, respectively, in vitro, showing that the "in vivo-in vitro gap" can be bridged [12].

Biological context of PTPRO

• Overexpression of PTPRO in A549 cells inhibited anchorage-independent growth, delayed reentry of the cells into the cell cycle after release from cell-cycle arrest, and increased susceptibility of the cells to apoptosis [1].
• The reduced expression of PTPRO in the primary lung tumors correlated with the methylation status of its CpG island [1].
• Whereas the epithelial PTPRO includes an approximately 800-amino acid extracellular domain, the major (3 kb) PTPROt cDNA predicts a unique 5' untranslated region and truncated (8 amino acids) extracellular domain with a conserved transmembrane region and single catalytic domain [13].
• The human PTPRO gene was assigned to human chromosome 1p35-pter using Southern blot analyses of genomic DNAs from rodent/human somatic hybrid cell lines containing human chromosome 1 or the p35-pter region of the chromosome [14].
• In kidney and brain, gene expression of PTP-U2 was detected as a 5.4 kb mRNA and in lung and placenta as 3.5 kb [15].

Anatomical context of PTPRO

• In fetal tissues, PTPRO expression was observed in the brain and lung, whereas lower levels were observed in the kidney [14].
• In adult tissues, PTPRO was less restricted and was observed in the lung, heart, skeletal muscle, prostate, testis, and in various areas of the brain, indicating that PTPRO expression is developmentally regulated [14].
• GLEPP1 PTPase protein is distributed to the podocyte foot processes themselves [16].
• The GLEPP1 PTPase domain shows homology with two other single domain transmembrane PTPases (PTP beta and Drosophila central nervous system PTP10D) [16].
• Histologic analysis of serial sections showed that the glomerular epithelial cells were linked to tubular epithelial cells, and some of these extended toward the medulla [17].

Associations of PTPRO with chemical compounds

• A novel PTP, termed protein tyrosine phosphatase receptor omicron (PTPRO), which is related to the homotypically adhering kappa, mu and PCP-2 receptor-type tyrosine phosphatases, was identified and characterized [14].
• Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in primary focal segmental glomerulosclerosis [3].
• Glomerular visceral epithelial cells are endowed with a sialic acid-rich surface coat (the "glomerular epithelial polyanion"), which in rat tissue contains the sialoprotein podocalyxin [18].
• These data indicate that xyloside induces a dramatic imbalance in the de novo-synthesized PGs of cellular and extracellular compartments and that cellular accumulation of xylosylated (sulfated) PGs selectively alters the Golgi apparatus of the glomerular epithelial cell, the cell that actively synthesizes PGs [19].
• These results suggest that GBM CS-heparan sulfate proteoglycan alterations consisting of either decreased number and/or less anionic charge occur early in PAN and support a role for glomerular epithelial cell maintenance of GBM CS for normal glomerular function [9].
• Treatment with tamoxifen increased PTPRO expression [20].

Co-localisations of PTPRO

• ACE2 co-localized with glomerular epithelial cell (podocyte) markers, and its localization within the podocyte was confirmed by immunogold labeling [21].

Regulatory relationships of PTPRO

• Extracellular matrix regulates proliferation and phospholipid turnover in glomerular epithelial cells [22].
• Human glomerular epithelial cell express CD4 and interaction with gp120 protein promotes PYK2 tyrosine phosphorylation [23].

Other interactions of PTPRO

• The extracellular domain of PTP-U2 contains 14 putative N-glycosylation sites and eight repeats of fibronectin type III-like motif [15].
• These data suggest that PTP-U2 is structurally similar to HPTP beta and DPTP10D, which have been reported previously [15].
• Human glomerular epithelial protein 1 (GLEPP1), a receptor-like membrane protein tyrosine phosphatase (PTPase), was cloned and sequenced from a human renal cortical cDNA library [24].
• Glomerular epithelial protein 1 and podocalyxin-like protein 1 in inflammatory glomerular disease (crescentic nephritis) in rabbit and man [2].
• With differentiation over 48 h an increase in IGFBP-2 and WT1 gene expression by Northern blot analysis occurred, and was localized by in situ hybridization to the differentiating glomerular epithelial cell mass [25].

Analytical, diagnostic and therapeutic context of PTPRO

• GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. Identification, molecular cloning, and characterization in rabbit [16].
• Northern blot analysis revealed that there were two different transcripts for PTP-U2 [15].
• The GLEPP1 gene was assigned to human chromosome 12p12-p13 by fluorescence in situ hybridization [24].
• GLEPP1 distribution in human renal biopsy with inflammatory glomerular disease and crescent formation was examined by immunocytochemistry [2].
• Double label immunofluorescence, immunoelectron microscopy, and peroxidase immunohistochemistry were used to map the GLEPP1 distribution in the developing glomerulus and in minimal-change nephropathy (MCN), congenital nephrotic syndrome of the Finnish type, and focal-segmental glomerulosclerosis (FSGS) [4].

References