Disease relevance of PTP4A1

• Generation of PRL-3- and PRL-1-specific monoclonal antibodies as potential diagnostic markers for cancer metastases [1].
• Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer [2].
• In plasma from 35 women with pregnancy-induced hypertension (PIH) and 35 normal pregnant women both at 39 weeks of gestation, plasma prolactin levels were measured at 8.30 a.m. (PRL1) and 9.30 a.m. (PRL2) under basal conditions [3].
• We stably transfected human A549 lung cancer cells with several short hairpin RNAs for PRL-1 and found decreased invasive activity in the resulting clones compared with control cells [4].

High impact information on PTP4A1

• Total tyrosine FAK phosphorylation and Tyr397 phosphorylation levels were continuously elevated in PRL-1 knockdown cells plated on fibronectin [4].
• In immunofluorescence studies, reduction in PRL-1 seemed to decrease cell membrane protrusions with a reduction in actin fiber extensions in spite of continuous phosphorylation of Tyr397 FAK, which could reflect reduced adhesion turnover [4].
• In this study, we evaluated the role of PRL-1 in cell proliferation and metastatic processes in human lung cancer cells [4].
• These results support the hypothesis that PRL-1 plays an important role in maintaining the malignant phenotype by exploiting Src activation processes, and that PRL-1 could be a promising therapeutic target for cancer metastasis and cell growth [4].
• PRL-3 and PRL-1 promote cell migration, invasion, and metastasis [5].

Biological context of PTP4A1

• Widespread expression of PRL-1 and -2 in multiple organ systems suggests an important functional role for these enzymes in normal tissue homeostasis [6].
• Cellular Localization of PRL-1 and PRL-2 Gene Expression in Normal Adult Human Tissues [6].
• PRL-1 is one of three closely related protein-tyrosine phosphatases, which are characterized by C-terminal farnesylation [7].
• The intron enhancer contributed significantly to PRL-1 promoter activity in HepG2 cells which contain PIEC but not to NIH 3T3 cells which do not [8].
• Here, we analyzed the structure of the human PRL-1 gene and localized it to chromosome 6 within band q12 [8].

Anatomical context of PTP4A1

• Human PRL-1, PRL-2, and PRL-3 tyrosine phosphatases induce the malignant transformation of epithelial cells [9].
• Here we show that PRL-1 mRNA is overexpressed in a number of human tumor cell lines, including HeLa cells [7].
• The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis [7].
• In mitotic cells PRL-1 relocalizes to the centrosomes and the spindle apparatus, proximal to the centrosomes, in a farnesylation-independent manner [7].
• We screened over 1,400 hybridoma clones to generate mAbs specific to each PRL member.RESULTS: We obtained two hybridoma clones specifically against PRL-3 and another two clones specifically against PRL-1 [1].

Associations of PTP4A1 with chemical compounds

• In the PRL-1 structure, a sulfate ion is bound to the active-site, providing stabilizing interactions to maintain the canonically found active conformation of PTPs, whereas the NMR structure exhibits an open conformation of the active-site [10].
• Neither the OV-1 nor the PRL-1 protein shares strong homology with any previously characterised phosphotyrosine phosphatase, suggesting that they probably belong to a new phosphatase family [11].
• When cells are treated with FTI-277, a selective farnesyltransferase inhibitor, PRL-1, -2, and -3 shifted into the nucleus [12].
• When cells were treated with brefeldin A, PRL-1 and -3 accumulated in a collapsed compact structure around the microtubule-organizing center [12].

Other interactions of PTP4A1

• PRL-2 was expressed heavily in almost every tissue and cell type examined, whereas PRL-1 expression levels varied considerably both between tissue types and between individuals [6].
• Cells stably transfected with PRL-1 or PRL-2 exhibited 2.7-3.3-fold increases over control cells in the rate of DNA synthesis and the proportion of cells in S-phase, and they progressed more rapidly from G1 into S [9].
• A 100-kb physical and transcriptional map around the EDH17B2 gene: identification of three novel genes and a pseudogene of a human homologue of the rat PRL-1 tyrosine phosphatase [11].
• The detailed structural information on the active enzyme conformation and regulation of PRL-1 provides the structural basis for the development of potential inhibitors of PRL enzymes [10].

Analytical, diagnostic and therapeutic context of PTP4A1

• Therefore, we investigated expression patterns for PRL-1 and -2 genes in multiple normal, adult human tissues using in situ hybridization [6].
• Using immunofluorescence we studied the subcellular localization of endogenous PRL-1, and our results demonstrate that PRL-1 exhibits cell cycle-dependent localization; in non-mitotic HeLa cells, PRL-1 is localized to the endoplasmic reticulum in a farnesylation-dependent manner [7].
• PRLF did not show any relation with neonatal morbidity, but PRL1 showed a significant direct relation with the Apgar score at 5 min [3].
• To prepare specific monoclonal antibody (MAb) against PRL-3, cDNAs of PRL-1, -2, and -3 were cloned by RT-PCR and inserted into prokaryotic expression vector pGEX-4T1, respectively [13].

References