| First Author | Cullis J | Year | 2014 |
| Journal | Cancer Cell | Volume | 25 |
| Issue | 2 | Pages | 181-95 |
| PubMed ID | 24525234 | Mgi Jnum | J:209645 |
| Mgi Id | MGI:5568272 | Doi | 10.1016/j.ccr.2014.01.025 |
| Citation | Cullis J, et al. (2014) The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1. Cancer Cell 25(2):181-95 |
| abstractText | 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. |
