Disease relevance of PTPRF

• 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 [1].
• Furthermore, rat mammary carcinomas with elevated neu expression (neu-induced) also had sharply elevated LAR-PTPase expression when compared to rat mammary carcinomas with little or no neu expression (7,12-dimethylbenzanthracene induced); the level of expression of LAR PTPase was directly correlated with the level of neu expression [2].
• Beta-catenin is tyrosine phosphorylated in three melanoma cell lines and associates with both the ErbB2 receptor tyrosine kinase and the LAR receptor tyrosine phosphatase [3].
• The cytoplasmic regions of HPTP beta, LCA, and LAR were expressed in Escherichia coli and purified to greater than 90% purity [4].
• The structure of the human leukocyte-common antigen-related molecule (LAR) protein tyrosine phosphatase gene was elucidated using phage and cosmid genomic DNA clones [5].

Psychiatry related information on PTPRF

• The EAR (0 to 3 hours) and the LAR (3 to 8 hours) were expressed as corresponding areas under the time-response curves [6].
• CONCLUSION: Negative physical and psychological states were related to low self-efficacy with the taking of immunosuppressive medication, non-compliance and subsequent LAR in our cohort of patients [7].
• At the present time it is likely that initiation of the inflammatory cascade leading to AFS is a multifactorial event, requiring the simultaneous occurrence of such things as IgE-mediated sensitivity (atopy), specific T-cell HLA receptor expression, exposure to specific fungi, and aberration of local mucosal defense mechanisms [8].

High impact information on PTPRF

• LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses [9].
• The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor [10].
• A human gene (LAR) that hybridizes to mouse leukocyte common antigen cDNA under relaxed hybridization conditions was isolated [11].
• The LAR gene is expressed in a broad range of cells, including T lymphocytes, kidney, and prostate cells [11].
• The structure of the protein encoded by the LAR gene was deduced by determining the nucleotide sequences of a 7.7-kb LAR cDNA [11].

Chemical compound and disease context of PTPRF

• The cytoplasmic domains of two human transmembrane protein tyrosine phosphatases (PTPases), LAR and CD45, have been expressed in Escherichia coli, purified to near-homogeneity, and compared for catalytic efficiency toward several phosphotyrosine-containing peptide substrates [12].
• Fourteen adult patients with bronchial asthma who were known late responders to bronchial allergen challenge were entered into a double-blind crossover study to compare the protective effects of nedocromil sodium (3 x 4 mg) and placebo aerosols on the late asthmatic response (LAR) [13].
• Using immunoprecipitation, sodium dodecyl sulfate gel electrophoresis, immunofluorescence and flow cytometry, we have studied the expression of LAR in human CD5+ B cells from chronic lymphocytic leukemia (B-CLL) patients [14].
• By use of recombinant enzymes, the effects of H2O2 on three PTPs [PTP1, LAR (leukocyte antigen-related), and VHR (vaccinia H1-related)] and three distinct serine/threonine protein phosphatases (PPs: PP2Calpha, calcineurin, and lambda phosphatase) were determined [15].
• We recently demonstrated that formoterol inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosinophilia in guinea pigs [16].

Biological context of PTPRF

• Assignment of TRIO, the Trio gene (PTPRF interacting) to human chromosome bands 5p 15.1-->p 14 by in situ hybridization [17].
• Our data suggest that increased expression and/or activity of LAR or related PTPs in insulin target tissues of obese humans may contribute to the pathogenesis of insulin resistance [18].
• Multiple isoforms of LAR, HPTP delta, and HPTP sigma appear to be generated by tissue-specific alternative splicing of up to four mini-exon segments that encode peptides of 4-16 aa located in both the extracellular and intracellular regions [19].
• Leukocyte common antigen-related (LAR) protein is a widely expressed receptor-type protein-tyrosine-phosphatase that is implicated in the regulation of intracellular signaling triggered by both cell adhesion and peptide growth factors [20].
• Interestingly, LAR expression significantly decreased the levels of disulfide-linked RET-MEN2A dimerization [20].

Anatomical context of PTPRF

• We propose that LAR and LIP.1 may regulate the disassembly of focal adhesions and thus help orchestrate cell-matrix interactions [21].
• Interestingly, ectopic expression of protein-tyrosine phosphatase (PTP) LAR inhibits epithelial cell migration by preventing phosphorylation and the increase in the free pool of beta-catenin; moreover, it inhibits tumor formation in nude mice [1].
• We propose that liprins function to localize LAR family tyrosine phosphatases at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates [22].
• LAR family transmembrane protein-tyrosine phosphatases function in axon guidance and mammary gland development [22].
• Liprin-alpha has LAR-independent functions in R7 photoreceptor axon targeting [23].

Associations of PTPRF with chemical compounds

• LAR is a broadly expressed transmembrane protein tyrosine phosphatase comprised of a cell adhesion-like ectodomain and two intracellular protein tyrosine phosphatase domains [21].
• Taken together, our results suggest that liprin autophosphorylation regulates its association with LAR [24].
• Endogenous LAR was shown to bind phosphorylated liprin-alpha1 from MDA-486 cells labeled in vivo with [32P]orthophosphate [24].
• The NH2-terminal region of the extracellular segment of the LAR protein contains three tandem Ig-like domains and nine non-Ig-like domains [11].
• The functional significance of a stretch of 10 highly conserved amino acid residues surrounding the critical cysteine residue located in the first domain of LAR was assessed [25].
• In hippocampal neurons, liprinalpha1 mutants that are immune to CaMKII degradation impair dendrite arborization, reduce spine and synapse number, and inhibit dendritic targeting of receptor tyrosine phosphatase LAR, which is important for dendrite development [26].

Physical interactions of PTPRF

• Liprin phosphorylation regulates binding to LAR: evidence for liprin autophosphorylation [24].
• The laminin-nidogen complex is a ligand for a specific splice isoform of the transmembrane protein tyrosine phosphatase LAR [27].
• The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains [28].

Enzymatic interactions of PTPRF

• LAR was phosphorylated by insulin receptor tyrosine kinase and autodephosphorylated by the catalytic activity of the PTPase domain 1 [29].

Other interactions of PTPRF

• The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions [21].
• Antibodies against specific IR phosphotyrosines indicated overlapping sites of action of PTP1B and LAR [30].
• Indirect immunofluorescent antibody staining revealed high expression of LAR in a punctate pattern, throughout the length of these cellular processes observed on laminin-nidogen [27].
• Rapid and irreversible inactivation of protein tyrosine phosphatases PTP1B, CD45, and LAR by peroxynitrite [31].
• The bimolecular reaction rates for CD45, LAR, and PTP1B were 2.0 x 10(8), 2.3 x 10(7), and 2.2 x 10(7) M(-1) s(-1), respectively [31].

Analytical, diagnostic and therapeutic context of PTPRF

• To obtain a better understanding of LAR function, we have characterized the mouse Ptprf gene as a first step toward site-directed mutagenesis studies in vitro and in vivo [32].
• These data suggest that LAR and similar receptor-like protein tyrosine phosphatases may contribute to the regulation of transmembrane signaling by selectively inhibiting the tyrosine phosphorylation of specific signal transducers that act downstream of the plasma membrane-associated tyrosine kinases [33].
• A physical association between LAR and the insulin receptor was then shown by immunoprecipitation of LAR from cell lysates and immunoblotting with antibody to the insulin receptor, or vice versa [34].
• By comparative RT-PCR, in situ hybridization, and Northern blot, LAR and FAP-1 mRNAs accumulation was found to be dose- and time-dependently increased by antiestrogens [35].
• LAR was increased an average of 6-fold in clonal lines of stably transfected cells, and cell fractionation confirmed its localization in the cell membrane [36].

References