Title : ( Physical Interaction between Embryonic Stem Cell-Expressed Ras (ERas) and Arginase-1 in Quiescent Hepatic Stellate Cells )
Authors: Silke Pudewell , Jana Lissy , Hossein Nakhaeizadeh , Mohamed S. Taha , Mohammad Akbarzadeh , Soheila Rezaei Adariani , Saeideh Nakhaeirad , Junjie Li , Claus Kordes , Dieter Haussinger , Roland P. Piekorz , Miriam M. Cortese-Krott , Mohammad Reza Ahmadian ,Abstract
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.
Keywords
, arginase 1; ARG1; embryonic stem cell, expressed Ras; ERas; hepatic stellate cells; quiescence; iNOS; L, arginine; L, ornithine; polyamines; spermidine; spermine; urea cycle@article{paperid:1089269,
author = {Silke Pudewell and Jana Lissy and Hossein Nakhaeizadeh and Mohamed S. Taha and Mohammad Akbarzadeh and Soheila Rezaei Adariani and Nakhaeirad, Saeideh and Junjie Li and Claus Kordes and Dieter Haussinger and Roland P. Piekorz and Miriam M. Cortese-Krott and Mohammad Reza Ahmadian},
title = {Physical Interaction between Embryonic Stem Cell-Expressed Ras (ERas) and Arginase-1 in Quiescent Hepatic Stellate Cells},
journal = {Cells},
year = {2022},
volume = {11},
number = {3},
month = {January},
issn = {2073-4409},
pages = {1--16},
numpages = {15},
keywords = {arginase 1; ARG1; embryonic stem cell-expressed Ras; ERas; hepatic stellate cells; quiescence;
iNOS; L-arginine; L-ornithine; polyamines; spermidine; spermine; urea cycle},
}
%0 Journal Article
%T Physical Interaction between Embryonic Stem Cell-Expressed Ras (ERas) and Arginase-1 in Quiescent Hepatic Stellate Cells
%A Silke Pudewell
%A Jana Lissy
%A Hossein Nakhaeizadeh
%A Mohamed S. Taha
%A Mohammad Akbarzadeh
%A Soheila Rezaei Adariani
%A Nakhaeirad, Saeideh
%A Junjie Li
%A Claus Kordes
%A Dieter Haussinger
%A Roland P. Piekorz
%A Miriam M. Cortese-Krott
%A Mohammad Reza Ahmadian
%J Cells
%@ 2073-4409
%D 2022