Disease relevance of PTPRU

• The identification of specific binding partners for this receptor-like PTP provides insight into the mechanisms of its biological action and suggests a role for hPTPkappa in the regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis [1].
• DNA sequences encoding a novel member of the receptor protein tyrosine phosphatase (R-PTP) family, termed PCP-2, were identified in a human pancreatic adenocarcinoma cDNA library [2].
• Molecular cloning and characterization of a novel human receptor protein tyrosine phosphatase gene, hPTP-J: down-regulation of gene expression by PMA and calcium ionophore in Jurkat T lymphoma cells [3].
• Synaptopodin expression correlated with the severity of proteinuria and with GLEPP1 expression [4].
• A PTP produced by the Yersinia bacteria (which can cause bubonic plague, septicemia and enteric diseases) is thought to be used as a 'weapon' against host cell functions [5].

High impact information on PTPRU

• Structure-function analysis of CD45 and other PTPs has identified structural features of PTP catalytic domains required for enzymatic activity [6].
• Two members of the Src-family of protein tyrosine kinases (PTKs), the p56lck and p59fyn proteins, have been implicated as physiological substrates of CD45, providing an important clue to how the action of this leukocyte-specific PTP might influence signaling by the T cell antigen receptor [6].
• The PTP superfamily enzymes, which include tyrosine-specific, dual specificity, low-molecular-weight, and Cdc25 phosphatases, are key mediators of a wide variety of cellular processes, including growth, metabolism, differentiation, motility, and programmed cell death [7].
• Unlike most members of the PTP superfamily, PTEN utilizes the phosphoinositide second messenger, phosphatidylinositol 3,4,5-trisphosphate (PIP3), as its physiologic substrate [7].
• Recently, myotubularin, a second PTP superfamily enzyme associated with human disease, has also been shown to utilize a phosphoinositide as its physiologic substrate [7].

Chemical compound and disease context of PTPRU

• We have previously identified a human receptor protein tyrosine phosphatase of the MAM domain family, termed PCP-2, in human pancreatic adenocarcinoma cells and found that this protein was colocalized with beta-catenin and E-cadherin at cell junctions [Wang, H.-Y., et al. (1996) Oncogene 12, 2555-2562] [8].
• However, PTP coexpression has no effect on the maturation of a surface glycoprotein of vesicular stomatitis virus [9].
• To investigate PTP substrate selectivity, we have set up a procedure to generate phage libraries that presents randomized, phosphotyrosine-containing peptides [10].
• In contrast to the conformational changes observed in the crystal structures of PTP1B and Yersinia PTP, the WPD loop (Trp419-Pro428) in the catalytic domain of SHP-1 moves away from the substrate binding pocket after binding the tungstate ion [11].
• One isolate, Selenomonas lacticifex, contained two distinct PTP-like phytase sequences, suggesting that multiple phytate hydrolyzing enzymes are present in this bacterium [12].

Biological context of PTPRU

• Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is a ubiquitous PTP implicated in the regulation of mitosis and cytoskeleton rearrangement [13].
• A potential role of PCP-2 in cell-cell recognition and adhesion is supported by its co-localization with cell adhesion molecules, such as catenin and E-cadherin, at sites of cell-cell contact [2].
• Upon transfection of PCP-2 cDNA into human embryonic kidney fibroblast 293 cells, a protein with an apparent Mr of 180 000 was detected by immunoblot analysis [2].
• Finally, we showed that PCP-2 was a negative regulator for cell migration [8].
• This study reports that PCP-2 was endogenously expressed at the cell surface and upregulated with increased cell density [8].

Anatomical context of PTPRU

• Protein tyrosine phosphatases (PTP) regulate the proliferation, differentiation, and viability of lymphocytes by modulating their signaling pathways [14].
• By using the differential display assay, we have cloned a putative receptor-type PTP, which is predominantly expressed in B-lymphoid tissues (lymph nodes and spleen) [14].
• These data support a function for PTP LAR in the regulation of epithelial cell-cell contacts at adherens junctions as well as in the control of beta-catenin signaling functions [15].
• In human umbilical vein endothelial cells (HUVECs) the PTP inhibitors phenylarsine oxide (PAO) and pervanadate induced proteolysis of the tight junction protein occludin [16].
• Based on these findings, it is suggested that some signaling pathways mediated by PMA and/or intracellular calcium are involved in the regulation of hPTP-J gene expression in Jurkat cells [3].

Associations of PTPRU 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 [17].
• Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in primary focal segmental glomerulosclerosis [4].
• The recently cloned type II receptor protein tyrosine phosphatase (RPTP) gene hPTP-J is a new member of the MAM (meprin, A5, PTPmicro) domain subfamily [18].
• Inhibition of PTP activity through reversible oxidation of the active-site cysteine residue is emerging as a general, yet poorly characterized, regulatory mechanism [19].
• In conclusion, PTPs are differentially oxidized at physiological pH and H(2)O(2) concentrations, and the PTP loop arginine is an important determinant for susceptibility to oxidation [20].

Physical interactions of PTPRU

• An in vivo binding assay revealed that PCP-2 could directly interact with beta-catenin through a region in the juxtamembrane domain [8].

Regulatory relationships of PTPRU

• We here provide evidence that TR-beta 1 but not TR-alpha 1 regulates the expression of the gene coding for PCP-2 in cerebellar Purkinje cells during neonatal rat development and that such regulation appears to be both T3 dependent and T3 independent [21].

Other interactions of PTPRU

• Thus PTP-LAR appears to play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may contribute to malignant progression and metastasis [15].
• In conclusion, interaction of PCP-2 with its substrate beta-catenin is involved in the process of cell-cell contact [8].
• The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins [22].
• RESULTS: There was decreased expression of four DSP genes (including PTEN); eight receptor PTP genes were downregulated in melanoma, among which were PTP-KAPPA and PTP-PI (consistent with our previous data) [23].
• Synaptopodin, GLEPP1, and nephrin were strongly expressed in normal kidney tissue [24].

Analytical, diagnostic and therapeutic context of PTPRU

• Molecular cloning and characterization of PTP pi, a novel receptor-like protein-tyrosine phosphatase [25].
• Site-directed mutagenesis, combined with detailed kinetic and mechanistic studies of Yersinia PTP, have contributed greatly to the understanding of the chemical mechanism for PTP catalysis, the nature of the enzymatic transition state, and the means by which the transition state is stabilized [26].
• Using degenerate oligonucleotides and the PCR, we have cloned a cDNA for an additional PTP, SH-PTP2, which contains two SH2 domains and is expressed ubiquitously [27].
• To determine the expression of various protein-tyrosine phosphatases (PTPs) in human gastric cancers, cDNAs encoding conserved PTP domains were amplified by reverse transcriptase polymerase chain reaction from KATO-III cell mRNA and sequenced [28].
• Guided by x-ray crystallography, molecular modeling, and enzyme kinetic analyses with wild type and mutant PTPs, we describe the development of a general, low molecular weight, non-peptide, non-phosphorus PTP inhibitor into an inhibitor that displays more than 100-fold selectivity for PTPbeta over PTP1B [29].

References