PTPRR, Cerebellum, and Motor Coordination

Schmitt, Imke; Bitoun, Emmanuelle; Manto, Mario

doi:10.1007/s12311-009-0118-4

Cited by 6 publications

(3 citation statements)

References 23 publications

(22 reference statements)

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“…This transdifferentiation has been shown to be driven by protein tyrosine phosphatases, which play a key role in neuronal development [ 25 ], including PTPRA [ 26 ] and PTPB1 [ 27 ]. Here, we found PTPRB (KSC p -value 0.937) and PTPRR (KSC p -value 0.939)—both are involved in neuronal differentiation [ 28 , 29 ] and thus may play a role in neuroendocrine differentiation. In addition, it is known that E-cadherin is downregulated by AR [ 30 ], and here we find its binding partner, CDH3 [ 31 ], may also be repressed directly by AR (KSC p -value = 0.957).…”

Section: Resultsmentioning

confidence: 93%

ORTI: An Open-Access Repository of Transcriptional Interactions for Interrogating Mammalian Gene Expression Data

Vafaee

Krycer

et al. 2016

PLoS ONE

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Transcription factors (TFs) play a fundamental role in coordinating biological processes in response to stimuli. Consequently, we often seek to determine the key TFs and their regulated target genes (TGs) amidst gene expression data. This requires a knowledge-base of TF-TG interactions, which would enable us to determine the topology of the transcriptional network and predict novel regulatory interactions. To address this, we generated an Open-access Repository of Transcriptional Interactions, ORTI, by integrating available TF-TG interaction databases. These databases rely on different types of experimental evidence, including low-throughput assays, high-throughput screens, and bioinformatics predictions. We have subsequently categorised TF-TG interactions in ORTI according to the quality of this evidence. To demonstrate its capabilities, we applied ORTI to gene expression data and identified modulated TFs using an enrichment analysis. Combining this with pairwise TF-TG interactions enabled us to visualise temporal regulation of a transcriptional network. Additionally, ORTI enables the prediction of novel TF-TG interactions, based on how well candidate genes co-express with known TGs of the target TF. By filtering out known TF-TG interactions that are unlikely to occur within the experimental context, this analysis predicts context-specific TF-TG interactions. We show that this can be applied to experimental designs of varying complexities. In conclusion, ORTI is a rich and publicly available database of experimentally validated mammalian transcriptional interactions which is accompanied with tools that can identify and predict transcriptional interactions, serving as a useful resource for unravelling the topology of transcriptional networks.

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Section: Resultsmentioning

confidence: 93%

ORTI: An Open-Access Repository of Transcriptional Interactions for Interrogating Mammalian Gene Expression Data

Vafaee

Krycer

et al. 2016

PLoS ONE

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“…It was found to be overexpressed in CRPC and the high expression was related to poor prognosis. This is extremely striking because PTPRR belongs to the family of protein tyrosine phosphatases (PTPs), which regulates proliferation, differentiation, and function of cancer cells by dephosphorylating tyrosine (for example, tyrosine in mitogen-activated (Noordman et al, 2006;Schmitt et al, 2009). Several studies have shown that the expression of PTPRR is decreased in several cancers including colorectal carcinomas, cervical cancer, and oral squamous cell carcinoma due to high methylation (Laczmanska et al, 2013;Su et al, 2013;Chang et al, 2014;Woźniak et al, 2014), suggesting a tumor suppressive role for PTPRR (Menigatti et al, 2009;Su et al, 2013;Duś-Szachniewicz et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods

Wang

Ren

2020

J. Zhejiang Univ. Sci. B

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To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosteroneregulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.

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“…According to the current knowledge, the PTPRR gene encodes a transmembrane protein known as protein tyrosine phosphatase receptor type R. It may be of particular relevance to the motor coordination function of the central nervous system and may be involved in oncogenesis in the digestive system, as gene knockout mice display an ataxia phenotype while PTPRR are epigenetically silenced in colorectal carcinoma (Menigatti et al, 2009). Further studies have shown that PTPRR is predominately expressed in adult mice cerebellum Purkinje cells, and involved in the function of the central nervous system by regulating ERK1/2 phosphorylation (Schmitt et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Protein Tyrosine Phosphatase Receptor Type R Accounts for the Progression of Hirschsprung Disease

Tian

Zeng

Tian

et al. 2019

Front. Mol. Neurosci.

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Hirschsprung disease (HSCR) is a common developmental disorder of the enteric nervous system (ENS). However, the disease mechanisms have not been fully elucidated. To better understand the etiology of HSCR, the role and mechanism of HSCR associated PTPRR (protein tyrosine phosphatase receptor-type R) in the multipotency of ENS progenitors and ENS development were explored. In the present study, the downregulated PTPRR expression in HSCR was reflected by microarray and validated by real-time PCR analyses. Moreover, PTPRR protein was mainly expressed in the cytoplasmic area of primary cultured ENS progenitors (Enteric neural crest cells, ENCCs) and significantly decreased after differentiation induction, which implies the anti-differentiation role in ENCCs. Further study employed an adenovirus transfection system. After genetic modulation, the ENCCs maintained undifferentiated patterns even in GDNF (Glial cell-line derived neurotrophic factor)-mediated directional differentiation, as well as significantly increased EdU positive immunofluorescence in the PTPRR overexpressing group while the development of the ENS was stunted in the PTPRR knockdown fetal gut. Moreover, the expression of ERK1/2 activated by GDNF was significantly decreased as reflected by western-blot or immunofluorescence analyses after genetic modulation in the PTPRR overexpressing group, which suggests the potential mechanism in regulating the MAPK/ERK1/2 pathway. Taken together, These data support the idea that PTPRR may ensure a certain number of neural precursor cells by inhibiting ENCC overt differentiation and maintaining ENCC proliferation, which is considered to be the multipotency of ENCCs, and eventually participate in the development of the ENS, and establish PTPRR protein as negative regulator of MAPK/ERK1/2 signaling cascades in neuronal differentiation and demonstrate their involvement in the pathophysiology of HSCR.

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PTPRR, Cerebellum, and Motor Coordination

Cited by 6 publications

References 23 publications

ORTI: An Open-Access Repository of Transcriptional Interactions for Interrogating Mammalian Gene Expression Data

ORTI: An Open-Access Repository of Transcriptional Interactions for Interrogating Mammalian Gene Expression Data

Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods

Downregulation of Protein Tyrosine Phosphatase Receptor Type R Accounts for the Progression of Hirschsprung Disease

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