Title : ( The Function of Embryonic Stem Cell-expressed RAS (E-RAS), a Unique RAS Family Member, Correlates with Its Additional Motifs and Its Structural Properties )
Authors: Saeideh Nakhaeirad , Hossein Nakhaeizadeh , Claus Kordes , Ion C. Cirstea , Malte Schmick , Radovan Dvorsky , Philippe I. H. Bastiaens , Dieter Haussinger , Mohammad Reza Ahmadian ,
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Abstract
E-RAS is a member of the RAS family specifically expressed in embryonic stem cells, gastric tumors, and hepatic stellate cells. Unlike classical RAS isoforms (H-, N-, and K-RAS4B), E-RAS has, in addition to striking and remarkable sequence deviations, an extended 38-amino acid-long unique N-terminal region with still unknown functions. We investigated the molecular mechanism of E-RAS regulation and function with respect to its sequence and structural features. We found that N-terminal extension of E-RAS is important for E-RAS signaling activity. E-RAS protein most remarkably revealed a different mode of effector interaction as compared with H-RAS, which correlates with deviations in the effector-binding site of E-RAS. Of all these residues, tryptophan 79 (arginine 41 in H-RAS), in the interswitch region, modulates the effector selectivity of RAS proteins from H-RAS to E-RAS features.
Keywords
, E, RAS; H, RAS; RAS protein; Raf kinase; effector selection; embryonic stem cell, expressed RAS; phosphatidylinositide 3, kinase (PI 3, kinase); phosphatidylinositol kinase (PI kinase); small GTPase; specificity determining residues
@article{paperid:1077971,
author = {Nakhaeirad, Saeideh and Hossein Nakhaeizadeh and Claus Kordes and Ion C. Cirstea and Malte Schmick and Radovan Dvorsky and Philippe I. H. Bastiaens and Dieter Haussinger and Mohammad Reza Ahmadian},
title = {The Function of Embryonic Stem Cell-expressed RAS (E-RAS), a Unique RAS Family Member, Correlates with Its Additional Motifs and Its Structural Properties},
journal = {Journal of Biological Chemistry},
year = {2015},
volume = {290},
number = {25},
month = {June},
issn = {0021-9258},
pages = {15892--15903},
numpages = {11},
keywords = {E-RAS; H-RAS; RAS protein; Raf kinase; effector selection; embryonic stem cell-expressed RAS; phosphatidylinositide 3-kinase (PI 3-kinase); phosphatidylinositol kinase (PI kinase); small GTPase; specificity determining residues},
}
%0 Journal Article
%T The Function of Embryonic Stem Cell-expressed RAS (E-RAS), a Unique RAS Family Member, Correlates with Its Additional Motifs and Its Structural Properties
%A Nakhaeirad, Saeideh
%A Hossein Nakhaeizadeh
%A Claus Kordes
%A Ion C. Cirstea
%A Malte Schmick
%A Radovan Dvorsky
%A Philippe I. H. Bastiaens
%A Dieter Haussinger
%A Mohammad Reza Ahmadian
%J Journal of Biological Chemistry
%@ 0021-9258
%D 2015
