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 Nakhaei-Rad Hossein Nakhaeizadeh Claus Kordes Ion C. Cirstea Malte Schmick Radovan Dvorsky Philippe I. H. Bastiaens Dieter H?ussinger Mohammad Reza Ahmadian |
| |
| Affiliation: | From the ‡Institute of Biochemistry and Molecular Biology II and ;§Clinic of Gastroenterology, Hepatology, and Infectious Diseases, Medical Faculty of the Heinrich-Heine University, 40255 Düsseldorf, ;the ¶Leibniz Institute for Age Research-Fritz Lipmann Institute, 07745 Jena, and ;the ‖Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany |
| |
| 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: | phosphatidylinositide 3-kinase (PI 3-kinase) phosphatidylinositol kinase (PI kinase) Raf kinase RAS protein small GTPase E-RAS effector selection H-RAS embryonic stem cell-expressed RAS specificity determining residues |
|
|
