scholarly journals Characterization of a murine gene encoding a developmentally regulated cytoplasmic dual-specificity mitogen-activated protein kinase phosphatase

2002 ◽  
Vol 364 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Robin J. DICKINSON ◽  
David J. WILLIAMS ◽  
David N. SLACK ◽  
Jill WILLIAMSON ◽  
Ole-Morten SETERNES ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Mammalian Cells ◽  
Critical Role ◽  
Nuclear Export Signal ◽  
Cellular Growth ◽  
Cell Fate Decisions ◽  
Isolation And Characterization ◽  
Dual Specificity ◽  
Mitogen Activated Protein

Mitogen-activated protein kinases (MAPKs) play a vital role in cellular growth control, but far less is known about these signalling pathways in the context of embryonic development. Duration and magnitude of MAPK activation are crucial factors in cell fate decisions, and reflect a balance between the activities of upstream activators and specific MAPK phosphatases (MKPs). Here, we report the isolation and characterization of the murine Pyst3 gene, which encodes a cytosolic dual-specificity MKP. This enzyme selectively interacts with, and is catalytically activated by, the ‘classical’ extracellular signal-regulated kinases (ERKs) 1 and 2 and, to a lesser extent, the stress-activated MAPK p38α. These properties define the ability of this enzyme to dephosphorylate and inactivate ERK1/2 and p38α, but not JNK (c-Jun N-terminal kinase) in vivo. When expressed in mammalian cells, the Pyst3 protein is predominantly cytoplasmic. Furthermore, leptomycin B causes a complete redistribution of the protein to the nucleus, implicating a CRM (chromosomal region maintenance)1/exportin 1-dependent nuclear export signal in determining the subcellular localization of this enzyme. Finally, whole-mount in situ hybridization studies in mouse embryos reveal that the Pyst3 gene is expressed specifically in the placenta, developing liver and in migratory muscle cells. Our results suggest that this enzyme may have a critical role in regulating the activity of MAPK signalling during early development and organogenesis.

scholarly journals Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Nimi Marcel ◽  
Apurva Sarin
Keyword(s):  
Cell Fate ◽  
Nuclear Export ◽  
Mammalian Cells ◽  
Cellular Response ◽  
T Regulatory Cells ◽  
Nuclear Export Signal ◽  
Ectopic Expression ◽  
Notch Pathway ◽  
Regulatory Cells ◽  
Cell Fate Decisions

Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1-/- Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation.

scholarly journals Protocol for nuclear export signal characterization of cGAS in mammalian cells

2021 ◽  
Vol 2 (3) ◽  
pp. 100649
Author(s):  
Yu Huang ◽  
Myles McLean ◽  
Chen Liang ◽  
Fei Guo
Keyword(s):  
Nuclear Export ◽  
Mammalian Cells ◽  
Nuclear Export Signal ◽  
Signal Characterization ◽  
Export Signal

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using in silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs. 

scholarly journals Isolation and characterization of multiple variants of recombinant human interleukin 4 expressed in mammalian cells.

1988 ◽  
Vol 263 (22) ◽  
pp. 10817-10823
Author(s):  
H V Le ◽  
L Ramanathan ◽  
J E Labdon ◽  
C A Mays-Ichinco ◽  
R Syto ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Interleukin 4 ◽  
Isolation And Characterization ◽  
Multiple Variants

scholarly journals Both Binding and Activation of p38 Mitogen-Activated Protein Kinase (MAPK) Play Essential Roles in Regulation of the Nucleocytoplasmic Distribution of MAPK-Activated Protein Kinase 5 by Cellular Stress

2002 ◽  
Vol 22 (20) ◽  
pp. 6931-6945 ◽  
Author(s):  
Ole Morten Seternes ◽  
Bjarne Johansen ◽  
Beate Hegge ◽  
Mona Johannessen ◽  
Stephen M. Keyse ◽  
...  
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Nuclear Export ◽  
Fluorescent Protein ◽  
Mapk Pathway ◽  
Nuclear Export Signal ◽  
Mitogen Activated Protein Kinase ◽  
Protein Fusion ◽  
Translational Machinery ◽  
Mitogen Activated Protein

ABSTRACT The p38 mitogen-activated protein kinase (MAPK) pathway is an important mediator of cellular responses to environmental stress. Targets of p38 include transcription factors, components of the translational machinery, and downstream serine/threonine kinases, including MAPK-activated protein kinase 5 (MK5). Here we have used enhanced green fluorescent protein fusion proteins to analyze the subcellular localization of MK5. Although this protein is predominantly nuclear in unstimulated cells, MK5 shuttles between the nucleus and the cytoplasm. Furthermore, we have shown that the C-terminal domain of MK5 contains both a functional nuclear localization signal (NLS) and a leucine-rich nuclear export signal (NES), indicating that the subcellular distribution of this kinase reflects the relative activities of these two signals. In support of this, we have shown that stress-induced activation of the p38 MAPK stimulates the chromosomal region maintenance 1 protein-dependent nuclear export of MK5. This is regulated by both binding of p38 MAPK to MK5, which masks the functional NLS, and stress-induced phosphorylation of MK5 by p38 MAPK, which either activates or unmasks the NES. These properties may define the ability of MK5 to differentially phosphorylate both nuclear and cytoplasmic targets or alternatively reflect a mechanism whereby signals initiated by activation of MK5 in the nucleus may be transmitted to the cytoplasm.

Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor

2003 ◽  
Vol 2 (6) ◽  
pp. 73
Author(s):  
Anthony J Saporita ◽  
Qiuheng Zhang ◽  
Neema Navai ◽  
Zehra Dincer ◽  
Junghyun Hahn ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Export Signal ◽  
Identification And Characterization
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