Mas oncogene signaling and transformation require the small GTP-binding protein Rac. Mol Cell Biol 1998 Mar;18(3):1225-35
Date
03/06/1998Pubmed ID
9488437Pubmed Central ID
PMC108835DOI
10.1128/MCB.18.3.1225Scopus ID
2-s2.0-0031935592 (requires institutional sign-in at Scopus site) 71 CitationsAbstract
The Mas oncogene encodes a novel G-protein-coupled receptor that was identified originally as a transforming protein when overexpressed in NIH 3T3 cells. The mechanism and signaling pathways that mediate Mas transformation have not been determined. We observed that the foci of transformed NIH 3T3 cells caused by Mas were similar to those caused by activated Rho and Rac proteins. Therefore, we determined if Mas signaling and transformation are mediated through activation of a specific Rho family protein. First, we observed that, like activated Rac1, Mas cooperated with activated Raf and caused synergistic transformation of NIH 3T3 cells. Second, both Mas- and Rac1-transformed NIH 3T3 cells retained actin stress fibers and showed enhanced membrane ruffling. Third, like Rac, Mas induced lamellipodium formation in porcine aortic endothelial cells. Fourth, Mas and Rac1 strongly activated the JNK and p38, but not ERK, mitogen-activated protein kinases. Fifth, Mas and Rac1 stimulated transcription from common DNA promoter elements: NF-kappaB, serum response factor (SRF), Jun/ATF-2, and the cyclin D1 promoter. Finally, Mas transformation and some of Mas signaling (SRF and cyclin D1 but not NF-kappaB activation) were blocked by dominant negative Rac1. Taken together, these observations suggest that Mas transformation is mediated in part by activation of Rac-dependent signaling pathways. Thus, Rho family proteins are common mediators of transformation by a diverse variety of oncogene proteins that include Ras, Dbl family, and G-protein-coupled oncogene proteins.
Author List
Zohn IE, Symons M, Chrzanowska-Wodnicka M, Westwick JK, Der CJAuthor
Magdalena Chrzanowska PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3T3 CellsActins
Animals
Cell Transformation, Neoplastic
Cytoskeleton
GTP Phosphohydrolases
GTP-Binding Proteins
Mice
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-raf
Receptors, G-Protein-Coupled
Retroviridae Proteins, Oncogenic
Signal Transduction
rac GTP-Binding Proteins
ras Proteins
rhoA GTP-Binding Protein
