Phosphatase of Regenerating Liver 2 (PRL2) Is Essential for Placental Development by Down-regulating PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) and Activating Akt Protein

Dong, Yongchun; Zhang, Lujuan; Zhang, Sheng; Bai, Yunpeng; Chen, Hanying; Sun, Xiao Xin; Yong, Weidong; Li, Wei; Colvin, Stephanie C.; Rhodes, Simon J.; Shou, Weinian; Zhang, Zhong Yin

doi:10.1074/jbc.m112.393462

Cited by 41 publications

(64 citation statements)

References 35 publications

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“…Decreased cell proliferation in PRL2 Ϫ/Ϫ placenta appears to be caused by Akt inactivation as a result of up-regulation of the tumor suppressor PTEN. These results provide the first evidence that PRL2 is required for extra-embryonic development by promoting cell proliferation via the PI3K-Akt signaling pathway (31).…”

mentioning

confidence: 60%

“…7, C and D). We previously reported that in placenta, PRL2 deficiency led to elevated PTEN expression, an antagonist of PI3K signaling pathway, and therefore decreased Akt activation (31). To examine whether this is also the case in testis, we measured PTEN protein level in germ cells isolated from wild-type and PRL2 Ϫ/Ϫ testes.…”

Section: Prl2 Deficiency Promotes Apoptosis In Germ Cellsmentioning

confidence: 99%

“…To determine where PRL2 is expressed in the testis, we took advantage of LacZ expression that is under the control of endogenous prl2 promoter in the mutant allele (31). Therefore, endogenous PRL2 transcription can be monitored by LacZ expression in heterozygous or homozygous PRL2 mutant mice.…”

Section: G-i) This Analysis Revealed That Sertoli Cell Development Wmentioning

confidence: 99%

“…Ϫ/Ϫ mice were previously described (31). Mice used in this study were all on a C57BL6/129P2 mixed genetic background.…”

Section: Animals-generation and Genotyping Of The Prl2mentioning

confidence: 99%

“…To define the biological function of the PRLs, we generated PRL2 knockout mice to study the effects of PRL deletion in a genetically controlled, organismal model. We previously reported that PRL2 deficiency causes growth retardation in both embryos and adult mice (31). The embryonic growth retardation was attributed to placenta insufficiency.…”

mentioning

confidence: 99%

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

Dong

Zhang

Bai

et al. 2014

Journal of Biological Chemistry

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Background:The PRLs are oncogenic when overexpressed but their physiological function is not well defined. Results: PRL2-deficient mice exhibit testis hypotrophy, decreased sperm production, and impaired reproductive potential. Conclusion: PRL2 promotes Kit signaling and germ cell survival by down-regulating PTEN. Significance: The study reveals the biological importance of PRL2 in spermatogenesis and identifies PRL2 as a novel target for cancer and male contraception.

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mentioning

confidence: 60%

Section: Prl2 Deficiency Promotes Apoptosis In Germ Cellsmentioning

confidence: 99%

Section: G-i) This Analysis Revealed That Sertoli Cell Development Wmentioning

confidence: 99%

“…Ϫ/Ϫ mice were previously described (31). Mice used in this study were all on a C57BL6/129P2 mixed genetic background.…”

Section: Animals-generation and Genotyping Of The Prl2mentioning

confidence: 99%

mentioning

confidence: 99%

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

Dong

Zhang

Bai

et al. 2014

Journal of Biological Chemistry

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PRL2/PTP4A2 Phosphatase Is Important for Hematopoietic Stem Cell Self-Renewal

et al. 2014

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Hematopoietic stem cell (HSC) self-renewal is tightly controlled by cytokines and other signals in the microenvironment. While stem cell factor (SCF) is an early acting cytokine that activates the receptor tyrosine kinase KIT and promotes HSC maintenance, how SCF/KIT signaling is regulated in hematopoietic stem cells is poorly understood. The protein tyrosine phosphatase 4A (PTP4A) family [aka PRL (phosphatase of regenerating liver) phosphatases], consisting of PTP4A1/PRL1, PTP4A2/PRL2 and PTP4A3/PRL3, represents an intriguing group of phosphatases implicated in cell proliferation and tumorigenesis. However, the role of PTP4A in hematopoiesis remains elusive. To define the role of PTP4A in hematopoiesis, we analyzed HSC behavior in Ptp4a2 (Prl2) deficient mice. We found that Ptp4a2 deficiency impairs HSC self-renewal as revealed by serial bone marrow transplantation assays. Moreover, we observed that Ptp4a2 null hematopoietic stem and progenitor cells (HSPCs) are more quiescent and show reduced activation of the AKT and ERK signaling. Importantly, we discovered that the ability of PTP4A2 to enhance HSPC proliferation and activation of AKT and ERK signaling depends on its phosphatase activity. Furthermore, we found that PTP4A2 is important for SCF-mediated HSPC proliferation and loss of Ptp4a2 decreased the ability of oncogenic KIT/D814V mutant in promoting hematopoietic progenitor cell proliferation. Thus, PTP4A2 plays critical roles in regulating HSC self-renewal and mediating SCF/KIT signaling.

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Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors

Kobayashi¹,

Nabinger²,

Bai

et al. 2017

Stem Cells

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The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors. While PRL2 deficiency resulted in moderate defects of thymopoiesis in the steady state, de novo generation of T cells from Prl2 null hematopoietic stem cells (HSCs) was significantly reduced following transplantation. Prl2 null HSPCs also showed impaired T cell differentiation in vitro. We found that Notch/RBPJ signaling upregulated PRL2 as well as c-Kit expression in T cell progenitors. Further, PRL2 sustains Notch-mediated c-Kit expression and enhances SCF/c-Kit signaling in T cell progenitors, promoting effective DN1-DN2 transition. Thus, we have identified a critical role for PRL2 phosphatase in mediating Notch and c-Kit signals in early T cell progenitors.

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Phosphatase of Regenerating Liver 2 (PRL2) Is Essential for Placental Development by Down-regulating PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) and Activating Akt Protein

Cited by 41 publications

References 35 publications

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

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

PRL2/PTP4A2 Phosphatase Is Important for Hematopoietic Stem Cell Self-Renewal

Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors

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