PTPRN Human

What is the genomic location and tissue expression pattern of PTPRN in humans?

PTPRN is located on human chromosome band 2q35 and demonstrates tissue-specific expression primarily in endocrine cells, neurons of the autonomic nervous system, and neuroendocrine neurons of the brain. Specifically, PTPRN expression has been detected in the pancreas, pituitary, adrenal medulla, amygdala, and hypothalamus - all tissues characterized by the presence of neurosecretory granules . PTPRN is a type I transmembrane protein with an inactive protein tyrosine phosphatase (PTP) domain, distinguishing it from other actively catalytic phosphatases .

What cellular processes does PTPRN regulate in human cells?

PTPRN participates in critical neuroendocrine processes, including biogenesis, transport, and regulation of exocytosis . Research has demonstrated that PTPRN significantly affects secretion pathways in various neuroendocrine cells, possibly by regulating hormone content and release mechanisms . Additionally, PTPRN plays a crucial role in diabetes-related processes, as revealed through gene screening experiments that highlighted its importance in the occurrence and development of diabetes mellitus .

How is PTPRN functionally distinct from other protein tyrosine phosphatases?

Unlike many protein tyrosine phosphatases that possess catalytic activity, PTPRN contains an inactive PTP domain . This structural distinction suggests that PTPRN's biological functions are mediated through protein-protein interactions rather than enzymatic dephosphorylation. Comparative analysis with other PTP family members, as outlined in search result data, indicates that PTPRN belongs to a subset of phosphatases that function primarily through non-catalytic mechanisms in cellular signaling cascades.

What is the evidence for PTPRN's role in glioma progression?

High expression of PTPRN has been correlated with poor prognosis in high-grade glioma patients . Experimental evidence demonstrates that PTPRN downregulation reduces proliferation and migration of glioma cells, while PTPRN overexpression induces these oncogenic phenotypes . In vivo studies using mouse xenograft models have shown that PTPRN knockdown significantly decreases tumor growth and improves survival rates . These findings collectively establish PTPRN as an important proliferation- and metastasis-promoting factor in glioma pathogenesis.

Through which molecular mechanisms does PTPRN promote tumor growth?

Research utilizing RNA-seq, co-immunoprecipitation, and mass spectrometry has revealed that PTPRN activates the PI3K/AKT pathway by interacting with HSP90AA1 . This interaction appears to be a critical mechanism through which PTPRN promotes cell proliferation and metastasis in glioma cells. The transcriptome analysis of U87 glioma cells following PTPRN knockdown has further elucidated downstream effectors of this signaling axis, providing potential targets for therapeutic intervention .

How do PTPRN expression levels correlate with clinical outcomes?

Clinical and prognostic analyses involving fifty-seven glioma patients have demonstrated that high PTPRN expression correlates with poor outcomes in high-grade glioma . Survival analysis using Kaplan-Meier curves has shown improved survival in mouse xenograft models following PTPRN downregulation, mirroring clinical observations . These findings suggest that PTPRN expression levels could serve as a prognostic biomarker in glioma patients and potentially in other neuroendocrine-related malignancies.

What are the recommended methods for modulating PTPRN expression in experimental models?

For cell transfection to downregulate PTPRN, short-hairpin RNA (shRNA) approaches have proven effective, with oligonucleotides targeting PTPRN ligated to pLKO.1 vector following standard procedures . For upregulation studies, overexpression plasmids constructed using cDNA from human glioma cell lines (such as U87) have been successfully employed . The recombinant plasmids containing the correct fragments can be recombined with lentivirus target plasmids using gateway methods with LR clonase . These approaches provide reliable tools for investigating PTPRN function in vitro.

What cell-based assays are most informative for studying PTPRN functions?

Several cell-based assays have demonstrated utility in evaluating PTPRN functions:

• Colony formation assay: This measures cell proliferation by culturing transfected cells for 14 days, followed by fixation with 4% paraformaldehyde and staining with 0.5% crystal violet .

• Wound healing assay: This quantifies cell migration by creating a scratch in confluent cell monolayers and monitoring closure over 24 hours in serum-free medium .

• In vivo xenograft models: These provide comprehensive assessment of tumor growth dynamics, with bioluminescence imaging and MRI serving as reliable methods for tumor volume quantification .

What approaches enable comprehensive analysis of PTPRN-dependent pathways?

RNA-seq analysis of cells following PTPRN knockdown has proven valuable for identifying PTPRN-regulated transcriptional networks . Additionally, co-immunoprecipitation (co-IP) combined with mass spectrometry has successfully identified protein interaction partners such as HSP90AA1, illuminating downstream signaling mechanisms . These omics-based approaches, coupled with pathway analysis tools, provide comprehensive insights into the cellular functions modulated by PTPRN.

How does PTPRN research relate to other protein tyrosine phosphatases in disease contexts?

While PTPRN has been specifically implicated in glioma biology, other protein tyrosine phosphatases have established roles in various human diseases. For instance, PTPN11 has definitive evidence linking it to Noonan syndrome and strong evidence for metachondromatosis . PTPN22 has limited evidence connecting it to IDDM 1 and rheumatoid arthritis, while PTPRC has strong evidence linking it to severe combined immunodeficiency . This comparative context helps researchers position PTPRN studies within the broader landscape of phosphatase biology in human disease.

What bioinformatic resources are recommended for PTPRN variant analysis?

For analyzing PTPRN variants, tools such as HOPE (Have yOur Protein Explained) can provide valuable insights into the potential consequences of amino acid substitutions . This approach has been successfully applied to other phosphatases like PTPN3, where the p.Q447K variant was analyzed for structural and functional implications . Additionally, researchers should consider utilizing freely available R packages for transcriptome analysis, as detailed in supplementary materials referenced in result , which provide workflows for analyzing gene expression data in pathophysiological conditions.

What is the evidence supporting PTPRN as a therapeutic target?

Experimental evidence strongly suggests that reducing PTPRN expression in glioma cells represents a promising therapeutic strategy . In vitro studies have demonstrated that PTPRN knockdown reduces proliferation and migration of glioma cells, while in vivo experiments have shown decreased tumor growth and improved survival in mouse xenograft models . The identification of PTPRN's interaction with HSP90AA1 and subsequent activation of the PI3K/AKT pathway provides a mechanistic rationale for therapeutic targeting .

What methodological approaches could facilitate PTPRN-targeted therapy development?

Development of PTPRN-targeted therapies could employ several methodological approaches:

• RNA interference (RNAi) strategies: The successful application of short-hairpin RNA for PTPRN knockdown in experimental models suggests that RNAi-based therapeutics might be effective .

• Small molecule inhibitors: Given PTPRN's interaction with HSP90AA1, compounds disrupting this protein-protein interaction could represent viable therapeutic candidates.

• Combination approaches: Since PTPRN activates the PI3K/AKT pathway, combining PTPRN-targeted therapies with existing PI3K/AKT inhibitors might yield synergistic effects.

How might PTPRN biomarker status inform precision medicine approaches?

The correlation between high PTPRN expression and poor prognosis in high-grade glioma suggests that PTPRN could serve as both a prognostic biomarker and a predictive indicator of therapeutic response . Implementation in precision medicine would require development of standardized assays for PTPRN quantification in clinical samples. Additionally, stratifying patients based on PTPRN expression levels could inform treatment decisions, particularly for therapies targeting PTPRN-dependent pathways such as PI3K/AKT signaling.