Disease relevance of PTPN7

• The determined structures together with the established SAR (structure-activity relationship) propose new avenues for the development of selective inhibitors that may have therapeutic potential for treating neurodegenerative diseases in the case of PTPRR or acute myeloblastic leukaemia targeting PTPN7 [1].
• FISH analysis of a patient with myelodysplastic syndrome characterized by myeloid hypoplasia and monocytosis reveals triplication of the HePTP gene on one allele with elevated protein expression in neoplastic myelomonocytic cells [2].
• Fluorescent in situ hybridization revealed that the human LC-PTP gene is located on the chromosome region 1q32.1, which is known to be a site associated with chromosomal deletion in malignant lymphomas, where candidate tumor suppressor genes might be present [3].
• The results of a DNA macroarray analysis showed that TPT enhanced the expression of G-CSFR and certain other neutrophil functional proteins, including CD14 and myeloid leukemia cell differentiation protein (MCL-1), and that TPT induced a decrease in expression of LC-PTP, leukocyte protein-tyrosine phosphatase, to about half the control level [4].

High impact information on PTPN7

• In intact T cells, HePTP-S225A enhanced T-cell receptor (TCR)-induced NFAT/AP-1 transactivation, while the acidic substitution mutant was as efficient as wild-type HePTP [5].
• Lipid raft targeting of hematopoietic protein tyrosine phosphatase by protein kinase C theta-mediated phosphorylation [5].
• Tyr185 dephosphorylation by the hematopoietic protein-tyrosine phosphatase (HePTP) represents an important mechanism for down-regulating ERK2 activity [6].
• To avoid nonspecific tyrosine dephosphorylation, HePTP employs Thr106 in the substrate recognition loop as a key negative determinant to restrain its protein-tyrosine phosphatase activity [6].
• Our results suggest that substrate specificity is conferred upon HePTP by both negative and positive selections [6].

Biological context of PTPN7

• In the PTPN7 structure, the WPD loop was in the closed conformation and part of the KIM (kinase-interaction motif) was visible, which forms an N-terminal aliphatic helix with the phosphorylation site Thr66 in an accessible position [1].
• A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1 [2].
• These observations prompted us to examine the experimental effects on cell growth of HePTP overexpression [2].
• The predicted open reading frame encodes a approximately 40-kDa protein composed of 360 amino acids and has no apparent hydrophobic segments, suggesting that it is a nontransmembrane PTP, which was designated as LC-PTP (leukocyte PTP) [3].
• The LC-PTP gene is organized into 11 exons, including the 5'-noncoding first exon and the 3'-noncoding exon [7].

Anatomical context of PTPN7

• Overexpression of hematopoietic protein-tyrosine phosphatase (HePTP) results in suppression of T lymphocyte activation as measured by T cell antigen receptor-induced activation of transcription factors binding to the 5' promoter of the interleukin-2 gene [8].
• In Jurkat cells, LC-PTP suppressed the ERK and p38 mitogen-activated protein kinase cascades [9].
• We conclude that amplification and overexpression of HePTP may be an important cofactor contributing to abnormal myeloid cell growth [2].
• Though normal myeloid cells show minimal HePTP expression, all hematopoietic cell lines tested show high expression of HePTP [2].
• Gene transfer of HePTP into NIH 3T3 cells was therefore performed, which caused altered cell morphology, disorganized growth, anchorage independent colony formation and subtle differences in the pattern of tyrosine phosphoproteins compared to control cell lines [2].

Associations of PTPN7 with chemical compounds

• Protein tyrosine phosphatases PTPN5, PTPRR and PTPN7 comprise a family of phosphatases that specifically inactivate MAPKs (mitogen-activated protein kinases) [1].
• To gain insight into the molecular basis for HePTP substrate specificity, we analyzed the effects of altering structural features unique to HePTP on the HePTP-catalyzed hydrolysis of p-nitrophenyl phosphate, Tyr(P) peptides, and its physiological substrate ERK2 [6].

Physical interactions of PTPN7

• This result indicates that phosphorylation of Tyr185 is important for ERK2 substrate recognition and that binding of the Elk-1 peptide substrate to ERK2/pTpY blocks the accessibility of pTyr185 to HePTP for dephosphorylation [10].

Enzymatic interactions of PTPN7

• LC-PTP dephosphorylated ERK2 in vitro [9].

Regulatory relationships of PTPN7

• Taken collectively, these results indicate that LC-PTP suppresses mitogen-activated protein kinase directly in vivo [9].

Other interactions of PTPN7

• On the other hand, the wild-type LC-PTP did not suppress the phosphorylation of sevenmaker ERK2 mutant [9].
• In Jurkat cells overexpressing LCPTP, a small fraction of cell ERK1 can be immunoprecipitated in stable association with LCPTP [11].

Analytical, diagnostic and therapeutic context of PTPN7

• Northern blot analysis revealed that the LC-PTP mRNA was preferentially expressed in a variety of hematopoietic cells and the transcriptional sizes were approximately 4.0 kilobases and approximately 2.9 kilobases [3].
• Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP [3].

References