A novel potential effector of M-Ras and p21 Ras negatively regulates p21 Ras-mediated gene induction and cell growth

Oncogene
G R EhrhardtJohn W Schrader

Abstract

Here, we report the identification and characterization of a new member of the RalGDS-family, which is widely expressed and interacts strongly and selectively with the GTP-bound forms of M-Ras and p21 Ras. This Ras pathway modulator (RPM), also termed RGL3, exhibited Ras-binding and catalytic domains typical of the RalGDS-family of guanine nucleotide exchange factors, and was most similar to Rlf (RalGDS-like factor), but was distinguished by a unique proline-rich region with multiple candidate SH3-domain binding sites. RPM/RGL3 resembled AF-6 and Nore1 in interacting strongly with constitutively active M-Ras and p21 Ras. In contrast to Rlf, transiently expressed RPM/RGL3 did not activate an Elk-1-inducible reporter gene alone or in combination with activated p21 Ras, but strongly inhibited induction of this reporter gene by co-expression of activated H-Ras or MEKK-1. This inhibitory effect was independent of the Ras binding domain and required a second signal provided by p21 Ras or MEKK-1, but not Raf-1 or M-Ras. Expression of RPM/RGL3 also strongly inhibited cell growth of fibroblasts transformed by an activated Src Y527F. Thus, RPM/RGL3 is a novel potential effector of both p21 Ras and M-Ras with the novel function of negativ...Continue Reading

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Citations

Oct 18, 2002·Experimental Hematology·Annette EhrhardtJohn W Schrader
Sep 16, 2004·Science's STKE : Signal Transduction Knowledge Environment·John Colicelli
Sep 19, 2006·Molecular and Cellular Biology·Nelson Nuñez RodriguezAndrew M-L Chan
May 15, 2004·Molecular and Cellular Biology·Pablo Rodriguez-VicianaFrank McCormick
May 19, 2010·Cellular Signalling·Elisa Ferro, Lorenza Trabalzini
Nov 29, 2011·Journal of Cellular Biochemistry·Ariel F CastroLawrence A Quilliam
Jul 9, 2002·Biochemical and Biophysical Research Communications·Mitsunobu Hoshino, Shun Nakamura
Jul 8, 2016·Scientific Reports·Tea KaartokallioHannele Laivuori
Jan 10, 2018·Cold Spring Harbor Perspectives in Medicine·Lucy C Young, Pablo Rodriguez-Viciana
Jun 11, 2002·American Journal of Physiology. Cell Physiology·J E DumontC Maenhaut
Feb 20, 2018·Critical Reviews in Biochemistry and Molecular Biology·Saeideh Nakhaei-RadMohammad Reza Ahmadian
May 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanling LiuGötz R A Ehrhardt
Apr 16, 2005·The Journal of Biological Chemistry·Mitsunobu HoshinoShun Nakamura

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