Disease relevance of PTPRJ

• The purpose of this study was to determine whether common variants in the PTPRJ gene represent low penetrance breast cancer susceptibility alleles [1].
• These results indicate that the genotypic profile of PTPRJ affects susceptibility to thyroid carcinomas, and that allelic loss of this gene is involved in thyroid carcinogenesis [2].
• Here we report the loss of heterozygosity (LOH) of PTPRJ in 11/76 (14.5%) informative thyroid tumors (including adenomas and carcinomas) [2].
• Its human homologue PTPRJ is frequently deleted in several cancer types, including colorectal cancer [3].
• It has been demonstrated that PTPRJ, the human homologue of Ptprj, is involved in the control of cell growth and adhesion, being furthermore altered in several types of cancer including mammary, thyroid, lung, colon, and pancreatic cancers [4].

Psychiatry related information on PTPRJ

• METHODS: Ten normal males slept for 6 nights in the laboratory: 1 adaptation (AD), 2 baseline (BSL, BSL-A), 2 selective Slow-Wave Sleep (SWS) deprivation (DEP-1, DEP-2), and 1 recovery night (REC) [5].

High impact information on PTPRJ

• In human colon, lung and breast cancers, we show frequent deletion of PTPRJ, allelic imbalance in loss of heterozygosity (LOH) and missense mutations [6].
• Here we report the positional cloning of the mouse gene Scc1 (Susceptibility to colon cancer 1) and the identification of Ptprj, encoding a receptor-type protein tyrosine phosphatase, as the underlying gene [6].
• DEP-1 amplifies in the developing vulva and the excretory system the small differences in the amount of EGF signal received by equivalent precursor cells to achieve binary cell fate decisions [7].
• The peptide sequence shows similarity also with the cell-density enhanced protein tyrosine phosphatase-1 (DEP-1/CD148), which is expressed on the sensory epithelia of the inner ear and on endothelial cells [8].
• CD148 is a receptor-like protein tyrosine phosphatase up-regulated on T cells after T cell receptor (TCR) stimulation [9].

Chemical compound and disease context of PTPRJ

• The expression of the phosphotyrosine phosphatase DEP-1/PTPeta dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation [10].

Biological context of PTPRJ

• Thus, carrying a specific PTPRJ haplotype confers a protective effect on the risk of breast cancer [1].
• We found that the PTPRJ genotypes homozygous for the Gln276Pro and Arg326Gln polymorphisms, and the Asp872 allele were more frequent in thyroid carcinoma patients than in healthy individuals (P=0.032) [2].
• We also looked for the Gln276Pro, Arg326Gln and Asp872Glu polymorphisms in exons 5, 6 and 13 of PTPRJ in 88 patients with thyroid tumors and in 54 healthy individuals [2].
• In addition, PTPRJ LOH was more frequent in thyroid carcinomas of heterozygotes for Gln276Pro and Arg326Gln compared with homozygotes (P=0.006) [2].
• In conclusion, the data presented show that CD148 corresponds to a previously described protein tyrosine phosphatase HPTP-eta/DEP-1 and that this molecule is involved in signal transduction in lymphocytes [11].

Anatomical context of PTPRJ

• To investigate the cellular function of DEP-1, stable cell lines inducibly expressing DEP-1 were generated [12].
• These results demonstrate that DEP-1 is a negative regulator of cell proliferation, cell-substratum contacts, motility and chemotaxis in fibroblasts [12].
• Together these data suggest an important role for DEP-1 in the function of cell-cell contacts and adherens junctions [13].
• Time-lapse interference reflection microscopy of live cells revealed that although small focal contacts at the leading edge were generated in DEP-1-expressing cells, they failed to mature into stable focal adhesions, as found in control cells [12].
• Using a tetracycline-inducible expression system, we show that the TCR-mediated activation of both the Ras and calcium pathways was inhibited by expression of CD148 at levels that approximate those found in activated primary T cells [14].

Associations of PTPRJ with chemical compounds

• The sequence obtained from N-terminus as well as from two different CNBr-digested peptides showed a close identity with a previously described tyrosine phosphatase named HPTP-eta/DEP-1 [11].
• Following expression of DEP-1 cDNA in COS cells a glycoprotein of 180 kDa was detected and PTP activity was demonstrated in immunocomplexes with a C-terminal peptide antiserum [15].
• The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase [16].
• These data suggest a possible mechanism of DEP-1 regulation in tumor cell lines involving serine/threonine and/or tyrosine phosphorylation [16].
• The responsiveness to somatostatin correlated with the expression of the phosphotyrosine phosphatase DEP-1/PTPeta, identified in C6 and U87MG cells, in which somatostatin inhibited cell growth [10].

Physical interactions of PTPRJ

• DEP1 also interacted with other members of the catenin gene family including beta-catenin and gamma-catenin [13].
• Recent studies have shown that CD148 interacts with the PDZ domain-containing protein syntenin, raising the possibility that its function or its localization with substrates in T and B cells may be controlled through this or a related interaction with another PDZ domain protein [17].
• We have shown that in epithelial cells the trapping mutant of DEP-1 interacts with the tight junction proteins occludin and ZO-1 in a tyrosine phosphorylation-dependent manner [18].

Enzymatic interactions of PTPRJ

• Pulldown and in vitro dephosphorylation assays confirmed our prediction and demonstrated an overall specificity of DEP-1 in targeting the phosphorylated tyrosine 204 of ERK1/2 [19].

Regulatory relationships of PTPRJ

• Overexpression of CD148 in the Jurkat T-cell line inhibited activation of the transcription factor nuclear factor of activated T cells following T-cell receptor (TCR) stimulation but not following stimulation through a heterologously expressed G protein-coupled receptor, the human muscarinic receptor subtype 1 [14].
• Somatostatin treatment increased the activity of DEP-1/PTPeta and inhibited ERK1/2 activation [10].
• CD148 has been shown to regulate density-dependent inhibition of cell growth as well as cellular differentiation in nonhematopoietic cells and has been shown to regulate signal transduction processes in several nonlymphoid hematopoietic cell types [17].

Other interactions of PTPRJ

• Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation [14].
• Based on these results, we propose that CD148 negatively regulates TCR signaling by interfering with the phosphorylation and function of PLCgamma1 and LAT [14].
• On the other hand, resistance to PTPRJ may be part of the mechanism of RET oncogenic conversion secondary to the M918T mutation [20].
• Different classes of EGFR inhibitors may have different potential to improve local tumour control after fractionated irradiation: a study on C225 in FaDu hSCC [21].
• Finally we evaluated the requirement for DEP-1/PTPeta in somatostatin inhibition of cell proliferation in post-surgical specimens derived from different grade human gliomas [10].

Analytical, diagnostic and therapeutic context of PTPRJ

• Also, DEP-1 activity, detected in PTP assays of immunocomplexes, was increased in dense cell cultures [15].
• Endogenous DEP-1 was detected in WI-38 human embryonic lung fibroblasts by immunoblotting and immunocomplex PTP assays [15].
• Molecular cloning, characterization, and chromosomal localization of a novel protein-tyrosine phosphatase, HPTP eta [22].
• The chromosomal localization determined by fluorescence in situ hybridization showed that the HPTP eta gene was located at chromosome 11p11.2 on the short arm of chromosome 11, which is frequently lost or deleted in human carcinomas [22].
• Phosphorylation of DEP-1 increased significantly after treatment of cells with the PTP inhibitor pervanadate [16].

References