Physical Interaction between Embryonic Stem Cell-Expressed Ras (ERas) and Arginase-1 in Quiescent Hepatic Stellate Cells

Embryonic stem cell-expressed Ras (ERas) is an atypical constitutively active member of the Ras family and controls distinct signaling pathways, which are critical, for instance, for the maintenance of quiescent hepatic stellate cells (HSCs). Unlike classical Ras paralogs, ERas has a unique N-termin...

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Published in:Cells (Basel, Switzerland) Switzerland), 2022-02, Vol.11 (3), p.508
Main Authors: Pudewell, Silke, Lissy, Jana, Nakhaeizadeh, Hossein, Taha, Mohamed S, Akbarzadeh, Mohammad, Rezaei Adariani, Soheila, Nakhaei-Rad, Saeideh, Li, Junjie, Kordes, Claus, Häussinger, Dieter, Piekorz, Roland P, Cortese-Krott, Miriam M, Ahmadian, Mohammad Reza
Format: Article
Language:English
Subjects:
Affinity
Animals
ARG1
Arginase
Arginase - metabolism
arginase 1
Cell culture
Chromatography, Liquid
embryonic stem cell-expressed Ras
Embryonic Stem Cells - metabolism
Enzymes
ERas
hepatic stellate cells
Hepatic Stellate Cells - metabolism
Homeostasis
Humans
Lipids
Liquid chromatography
Liver
Mass spectroscopy
Nitric oxide
Oncogene Protein p21(ras) - metabolism
Polyamines
Polymerase chain reaction
Proteins
quiescence
Rats
Reagents
Spermidine
Spermine
Stellate cells
Stem cells
Tandem Mass Spectrometry
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Summary:Embryonic stem cell-expressed Ras (ERas) is an atypical constitutively active member of the Ras family and controls distinct signaling pathways, which are critical, for instance, for the maintenance of quiescent hepatic stellate cells (HSCs). Unlike classical Ras paralogs, ERas has a unique N-terminal extension (Nex) with as yet unknown function. In this study, we employed affinity pull-down and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses and identified 76 novel binding proteins for human and rat ERas Nex peptides, localized in different subcellular compartments and involved in various cellular processes. One of the identified Nex-binding proteins is the nonmitochondrial, cytosolic arginase 1 (ARG1), a key enzyme of the urea cycle and involved in the de novo synthesis of polyamines, such as spermidine and spermine. Here, we show, for the first time, a high-affinity interaction between ERas Nex and purified ARG1 as well as their subcellular colocalization. The inhibition of ARG1 activity strikingly accelerates the activation of HSCs ex vivo, suggesting a central role of ARG1 activity in the maintenance of HSC quiescence.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11030508