Phosphatase of Regenerating Liver 2 (PRL2) Deficiency Impairs Kit Signaling and Spermatogenesis

Dong, Yongchun; Zhang, Lujuan; Bai, Yunpeng; Zhou, Hong; Campbell, Amanda M.; Chen, Hanying; Yong, Weidong; Zhang, Wenjun; Zeng, Qi; Shou, Weinian; Zhang, Zhong Yin

doi:10.1074/jbc.m113.512079

Cited by 32 publications

(46 citation statements)

References 64 publications

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“…212 PRL2 and PRL3 were subsequently discovered by their sequence similarity to PRL1. Unlike many other PTPs that antagonize the action of protein kinases, the PRLs rank among the most oncogenic PTPs and function to promote activation of both ERK1/2 213–217 and Akt 218–221 , two of the key pathways that are abnormally up-regulated in cancer. PRLs are overexpressed in many cancer cell lines, and those with high level PRL expressions show increased proliferation, migration and anchorage-independent cell growth.…”

Section: Ptp Regulatory Mechanismsmentioning

confidence: 99%

Regulatory Mechanisms and Novel Therapeutic Targeting Strategies for Protein Tyrosine Phosphatases

Zhang

2017

Chem. Rev.

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Appropriate level of protein phosphorylation on tyrosine is essential for cells to react to extracellular stimuli and keep cellular homeostasis. Faulty operation of signal pathways mediated by protein tyrosine phosphorylation causes numerous human diseases, which presents enormous opportunities for therapeutic interventions. While the importance of protein tyrosine kinases in orchestrating the tyrosine phosphorylation networks and in target-based drug discovery has long been recognized, the significance of protein tyrosine phosphatases (PTPs) in cellular signaling and disease biology has historically been underappreciated, due to a large extent an erroneous assumption that they are largely constitutive and housekeeping enzymes. Here, we provide a comprehensive examination on a number of regulatory mechanisms including redox modulation, allosteric regulation, and protein oligomerization, in controlling PTP activity. These regulatory mechanisms are integral to the myriad PTP-mediated biochemical events and reinforce the concept that PTPs are indispensable and specific modulators of cellular signaling. We also discuss how disruption of these PTP regulatory mechanisms can cause human diseases and how these diverse regulatory mechanisms can be exploited for novel therapeutic development.

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Section: Ptp Regulatory Mechanismsmentioning

confidence: 99%

Regulatory Mechanisms and Novel Therapeutic Targeting Strategies for Protein Tyrosine Phosphatases

Zhang

2017

Chem. Rev.

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“…More recent in situ hybridization studies show ubiquitous PRL-2 mRNA expression across nearly all human tissues, suggesting that PRL-2 plays a role in fundamental physiological functions (Dumaual et al 2006). PRL-2 deficiency is associated with several altered phenotypes including increased serum Mg 2+ levels, decreased lymphocyte and neutrophil counts, and hypertrophy of the testicular germinal epithelium and placenta (Hardy et al 2014;Kobayashi et al 2014;Dong et al 2012Dong et al , 2014. PRL-2 knockouts also display elevated PTEN levels and decreased Akt phosphorylation (Dong et al 2012Stephens et al 2008).…”

Section: Introductionmentioning

confidence: 96%

Localizing PRL-2 expression and determining the effects of dietary Mg2+ on expression levels

Gungabeesoon

Tremblay

Uetani

2016

Histochem Cell Biol

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The phosphatase of regenerating liver (PRL) is a group of protein tyrosine phosphatases that play a key role in cancer progression and metastasis. We previously showed that PRL-2 modulates intracellular Mg(2+) levels and sustains cancer phenotypes by binding to the Mg(2+) transporter CNNM3. However, the physiological functions of PRL-2 in animals remain largely unknown. To better understand which cell types are associated with PRL-2 function, we characterized its expression in mouse tissues using a PRL-2 β-galactosidase reporter mouse model. Our results demonstrated that PRL-2 was ubiquitously expressed, with the highest expression levels observed in the hippocampal pyramidal neurons, ependymal cells, cone and rod photoreceptor cells, endocardium, vascular and bronchial smooth muscle, and collecting ducts in the kidney. On the other hand, PRL-2 expression was undetectable or very low in the parenchymal cells of the liver and pancreas. Our results also indicated that PRL-2 is involved in cell-type-specific Mg(2+) homeostasis and that PRL-2 expression is potentially inversely regulated by dietary Mg(2+) levels.

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“…Among the 3 PRLs, PRL2 is the most ubiquitously expressed in mammals (15,17). Moreover, analysis of PRL2-deficient mice revealed that PRL2 is required for proper placental development (18), spermatogenesis (19), and hematopoietic stem cell self-renewal (20).…”

Section: +mentioning

confidence: 99%

PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms

et al. 2017

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Phosphatase of Regenerating Liver 2 (PRL2) Deficiency Impairs Kit Signaling and Spermatogenesis

Cited by 32 publications

References 64 publications

Regulatory Mechanisms and Novel Therapeutic Targeting Strategies for Protein Tyrosine Phosphatases

Regulatory Mechanisms and Novel Therapeutic Targeting Strategies for Protein Tyrosine Phosphatases

Localizing PRL-2 expression and determining the effects of dietary Mg2+ on expression levels

PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms

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