Disease relevance of PTPN3

• Following the examination of 92 gastric cancer patients' pathological specimens, PTPN3 expression showed no statistical significance with respect to the patients' survival [1].
• The most closely-related gene to tyrosine phosphatase, PTPN3, has been shown to be mutated in cases of human colorectal cancer, but its expression is cases of gastric cancer is not known [1].
• PTPN3 and PTPN4 tyrosine phosphatase expression in human gastric adenocarcinoma [1].
• Interestingly, PTPH1 gene was mapped to 9q31 where the gene for Gorlin syndrome, a putative tumor suppressor gene, exists [2].
• We investigated the mRNA expression of cytosolic protein tyrosine phosphatase (PTPH1), which has a homologous domain to cytoskeletal-associated proteins, in human hepatocellular carcinomas (HCCs) by using reverse transcriptase-polymerase chain reaction (RT-PCR) [3].

High impact information on PTPN3

• The open reading frame predicts a protein of 913 amino acids (approximately 104 kDa), termed PTPH1 [4].
• PTPH1 is a predominant protein-tyrosine phosphatase capable of interacting with and dephosphorylating the T cell receptor zeta subunit [5].
• Furthermore, phorbol ester-stimulated shedding of the TACE substrate tumor necrosis factor-alpha was decreased in cells expressing catalytically active PTPH1 compared with inactive PTPH1 [6].
• Our results suggest that PTPH1 may exert its effects on cell growth through dephosphorylation of VCP, thus implicating tyrosine phosphorylation as an important regulator of VCP function [7].
• To identify the direct target of PTPH1 in the cell, we generated a substrate-trapping mutant, in which an invariant aspartate residue was changed to alanine (D811A in PTPH1) [7].

Biological context of PTPN3

• Ectopic expression of wild type PTPH1 dramatically inhibited cell growth, whereas a catalytically impaired mutant showed no effect [7].
• Like wild type PTPH1, this double mutant also inhibited cell proliferation [7].
• We have investigated the mRNA expression of 2 human protein tyrosine phosphatases with sequence homology to cytoskeletal proteins, PTPH1 and PTPMEG [2].
• Here we report that expression of PTPH1 in Jurkat T cells reduced the TCR-induced activation of reporter genes encompassing parts of the IL-2 gene promoter and driven by nuclear factor of activated T cells plus activator protein-1 [8].
• We also performed RT-PCR single-strand conformation polymorphism (SSCP) analysis in HCC cell lines and tissues in the C-terminal region of the catalytic domain of PTPH1 [3].

Anatomical context of PTPN3

• RESULTS: PTPN3 and PTPN4 were expressed in all gastric cancer cell lines and clinical cancer tissue specimens examined [1].
• PTPH1 mRNA was detected in all HCC cell lines (n = 6), and HCC and adjacent noncancerous tissues (n = 8) examined, indicating that PTPH1 was expressed in HCCs and hepatocytes [3].
• In contrast, the expression of PTPH1 mRNA was significantly increased in cancer lesions compared with that in normal mucosa [9].

Chemical compound and disease context of PTPN3

• PTPN3 is a membrane-associated tyrosine phosphatase with FERM, PDZ, and PTP domains previously implicated in regulating tyrosine phosphorylation of growth factor receptors and p97 VCP (valosin-containing protein, termed Cdc48 in Saccharomyces cerevisiae) and is mutated in a subset of colon cancers [10].

Associations of PTPN3 with chemical compounds

• Moreover, induction of wild type PTPH1 resulted in specific dephosphorylation of VCP without changing the overall phosphotyrosine profile of the cells [7].
• These results raise the possibility that 14-3-3beta may function as an adaptor molecule in the regulation of PTPH1 and may provide a link between serine/threonine and tyrosine phosphorylation-dependent signaling pathways [11].
• These results suggest that in addition to a potential role in controlling subcellular localization, the NH2-terminal band 4.1 homology domain of PTPH1 may exert a direct effect on catalytic function [12].

Regulatory relationships of PTPN3

• Expression of active PTPH1 also reduced receptor-induced activation of Erk2 MAP kinase, its upstream activator, Mek, and the Jnk kinases [8].
• CONCLUSION: This finding indicates that both PTPN3 and PTPN4 are expressed within human gastric cancer cells and that PTPN3 seems to play an important role in gastric cancer differentiation and the progression of malignancy [1].
• Binding of 14-3-3beta to PTPH1 in vitro was abolished by pretreating PTPH1 with potato acid phosphatase and was greatly enhanced by pretreating with Cdc25C-associated protein kinase [11].

Other interactions of PTPN3

• The interaction is mediated via binding of the PDZ domain of PTPH1 to the COOH terminus of TACE [6].
• Two novel motifs RSLS359VE and RVDS853EP in PTPH1 were identified as major 14-3-3beta-binding sites, both of which are distinct from the consensus binding motif RSXSXP recently found in Raf-1 [11].
• Expression of cytoskeletal-associated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma [3].
• Gene for the human transmembrane-type protein tyrosine phosphatase H (PTPRH): genomic structure, fine-mapping and its exclusion as a candidate for Peutz-Jeghers syndrome [13].
• PTPH1 is a human protein-tyrosine phosphatase with homology to the band 4.1 superfamily of cytoskeleton-associated proteins [12].

Analytical, diagnostic and therapeutic context of PTPN3

• Northern-blot analysis of PTPH1 using poly (A)+ RNA from normal human colon tissue showed a low-abundance message of 4.3 kb [2].
• Moreover, the chromosomal localization of PTPH1 gene was investigated by fluorescence in situ hybridization [2].

References