De novo synthesis of protein phosphatase 1A, magnesium dependent, alpha isoform (PPM1A) during oocyte maturation

Chuderland, Dana; Dvashi, Zeev; Kaplan-Kraicer, Ruth; Ben-Meir, Daniella; Shalgi, Ruth; Lavi, Sara

doi:10.2478/s11658-012-0022-7

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…22,71,72 Numerous modes of regulation were suggested to control PPM1A expression at both mRNA and protein levels. Several reports found elevated PPM1A transcription on cell differentiation, 22,73 and we have also recently found enhanced mRNA levels during oocyte maturation. 73 Alternatively, PPM1A could be regulated through its subcellular localization.…”

Section: Ppm1a Regulationsupporting

confidence: 77%

Protein Phosphatase Magnesium Dependent 1A Governs the Wound Healing–Inflammation–Angiogenesis Cross Talk on Injury

Dvashi

Shalom

Shohat

et al. 2014

The American Journal of Pathology

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Protein phosphatase magnesium dependent 1A (PPM1A) has been implicated in fibrosis and skin wounding. We generated PPM1A knockout mice to study the role of PPM1A in the wound healing-inflammation-angiogenesis cross talk. The role of PPM1A in these processes was studied using the ocular alkali burn model system. In the injured cornea the absence of PPM1A led to enhanced inflammatory response, stromal keratocyte transactivation, fibrosis, increased p38 mitogen-activated protein kinase phosphorylation, elevated expression of transforming growth factor-β-related genes (including Acta2, TGF-β, Col1, MMP9, and VEGF) and subsequently to neovascularization. Augmented angiogenesis in the absence of PPM1A is a general process occurring in vivo in PPM1A knockout mice upon subcutaneous Matrigel injection and ex vivo in aortic ring Matrigel cultures. Using primary keratocyte cultures and various experimental approaches, we found that phospho-p38 is a favored PPM1A substrate and that by its dephosphorylation PPM1A participates in the regulation of the transforming growth factor-β signaling cascade, the hallmark of inflammation and the angiogenic process. On the whole, the studies presented here position PPM1A as a new player in the wound healing-inflammation-angiogenesis axis in mouse, reveal its crucial role in homeostasis on injury, and highlight its potential as a therapeutic mediator in pathologic conditions, such as inflammation and angiogenesis disorders, including cancer.

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Section: Ppm1a Regulationsupporting

confidence: 77%

Protein Phosphatase Magnesium Dependent 1A Governs the Wound Healing–Inflammation–Angiogenesis Cross Talk on Injury

Dvashi

Shalom

Shohat

et al. 2014

The American Journal of Pathology

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“…Several evidences have pointed out diverse functions of the JNK pathway in germline homeostasis, meiosis progression and spindle assembly [49] – [51] . Additionally, a PP2C isoform (PPM1A) is synthesized during oocyte maturation in mammals [52] and the RhoA GTPase is involved in ovulation in Caenorhabditis elegans [53] . Another interacting partner of SmVKR1 is the transmembrane protein Notch, which is known to be involved in germline proliferation and meiosis progression [54] – [57] .…”

Section: Discussionmentioning

confidence: 99%

Venus Kinase Receptors Control Reproduction in the Platyhelminth Parasite Schistosoma mansoni

et al. 2014

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The Venus Kinase Receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G Protein Coupled Receptors. This receptor tyrosine kinase (RTK) was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a large variety of invertebrates. A single vkr gene is found in most genomes, except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a unique family of RTKs present only in invertebrates and their biological functions are still to be discovered. In this work, we show that SmVKRs are expressed in the reproductive organs of S. mansoni, particularly in the ovaries of female worms. By transcriptional analyses evidence was obtained that both SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr expression by RNA interference induced spectacular morphological changes in female worms with a strong disorganization of the ovary, which was dominated by the presence of primary oocytes, and a defect of egg formation. Following expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be activated by distinct ligands which are L-Arginine and calcium ions, respectively. Signalling analysis in Xenopus oocytes revealed the capacity of SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c-Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results of yeast two-hybrid experiments identifying several components of the JNK pathway as specific interacting partners of SmVKR1. In conclusion, these results demonstrate the functions of SmVKR in gametogenesis, and particularly in oogenesis and egg formation. By eliciting signalling pathways potentially involved in oocyte proliferation, growth and migration, these receptors control parasite reproduction and can therefore be considered as potential targets for anti-schistosome therapies.

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“…The JNK pathway was activated by SmVKR1 but not by SmVKR2, corroborating Y2H screening results which showed a specific interaction of SmVKR1 with Rho1, Mek7, and PP2C ( Vanderstraete et al, 2014 ). Since the JNK pathway has been shown to play a major role in oogenesis and meiosis resumption in Caenorhabditis elegans ( Smith et al, 2002 ), in Drosophila melanogaster ( Sackton et al, 2007 ), and in mammals ( Huang et al, 2011 ; Chuderland et al, 2012 ), it was postulated that it could be used as a pathway by SmVKR1 to influence oocyte maturation. Furthermore the implication of schistosome VKRs in oogenesis and spermatogenesis was demonstrated by RNA interference.…”

Section: Functions Of Schistosome Rtks In Reproductionmentioning

confidence: 99%

Receptor tyrosine kinases and schistosome reproduction: new targets for chemotherapy

et al. 2014

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Schistosome parasites still represent a serious public health concern and a major economic problem in developing countries. Pathology of schistosomiasis is mainly due to massive egg production by these parasites and to inflammatory responses raised against the eggs which are trapped in host tissues. Tyrosine kinases (TKs) are key molecules that control cell differentiation and proliferation and they already represent important targets in cancer therapy. During recent years, it has been shown that receptor tyrosine kinases (RTK) signaling was active in reproductive organs and that it could regulate sexual maturation of schistosomes and egg production. This opens interesting perspectives for the control of transmission and pathogenesis of schistosomiasis based on new therapies targeting schistosome RTKs. This review relates the numerous data showing the major roles of kinase signaling in schistosome reproduction. It describes the conserved and particular features of schistosome RTKs, their implication in gametogenesis and reproduction processes and summarizes recent works indicating that RTKs and their signaling partners are interesting chemotherapeutical targets in new programs of control.

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De novo synthesis of protein phosphatase 1A, magnesium dependent, alpha isoform (PPM1A) during oocyte maturation

Cited by 8 publications

References 38 publications

Protein Phosphatase Magnesium Dependent 1A Governs the Wound Healing–Inflammation–Angiogenesis Cross Talk on Injury

Protein Phosphatase Magnesium Dependent 1A Governs the Wound Healing–Inflammation–Angiogenesis Cross Talk on Injury

Venus Kinase Receptors Control Reproduction in the Platyhelminth Parasite Schistosoma mansoni

Receptor tyrosine kinases and schistosome reproduction: new targets for chemotherapy

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