| Literature DB >> 24525234 |
Jane Cullis1, David Meiri2, Maria Jose Sandi2, Nikolina Radulovich3, Oliver A Kent2, Mauricio Medrano1, Daphna Mokady2, Josee Normand2, Jose Larose2, Richard Marcotte2, Christopher B Marshall2, Mitsuhiko Ikura1, Troy Ketela4, Jason Moffat4, Benjamin G Neel5, Anne-Claude Gingras6, Ming-Sound Tsao1, Robert Rottapel7.
Abstract
Cellular transformation by oncogenic RAS engages the MAPK pathway under strict regulation by the scaffold protein KSR-1. Here, we report that the guanine nucleotide exchange factor GEF-H1 plays a critical role in a positive feedback loop for the RAS/MAPK pathway independent of its RhoGEF activity. GEF-H1 acts as an adaptor protein linking the PP2A B' subunits to KSR-1, thereby mediating the dephosphorylation of KSR-1 S392 and activation of MAPK signaling. GEF-H1 is important for the growth and survival of HRAS(V12)-transformed cells and pancreatic tumor xenografts. GEF-H1 expression is induced by oncogenic RAS and is correlated with pancreatic neoplastic progression. Our results, therefore, identify GEF-H1 as an amplifier of MAPK signaling and provide mechanistic insight into the progression of RAS mutant tumors.Entities:
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Year: 2014 PMID： 24525234 DOI： 10.1016/j.ccr.2014.01.025
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743