Synergism between two growth regulatory pathways: cooperative transformation of NIH3T3 cells by G alpha 12 and c-raf-1.
The alpha-subunit of the heterotrimeric G-protein, G12, has been shown to induce cellular transformation when overexpressed or oncogenically activated in rodent fibroblasts. To investigate the interaction between Galpha12 transforming pathway and the Ras-Raf-MAPK pathway, we examined the ability of mitogenic signaling molecules in cooperating with Galpha12 in transforming NIH3T3 fibroblasts. We observed a striking cooperative effect on focus-forming ability when Galpha12 and c-raf-1 cDNAs were co-transfected into NIH3T3 cells. NIH3T3 cells coexpressing both Galpha12 and c-raf-1 resulted in the constitutive activation of the mitogenic-activated protein kinase (MAPK). In addition, the levels of GTP-bound Ras were elevated in Galpha12 transformed NIH3T3 cells. Our results provide a model for studying the effects of simultaneous activation of two distinct growth regulatory pathways in cellular transformation.
Zhang
Y
Y
The Derald H Ruttenberg Cancer Center, The Mount Sinai Medical School, New York 10029, USA.
Saez
R
R
Leal
M A
MA
Chan
A M
AM
D016475:3T3 Cells / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005822:Genetic Vectors; D051379:Mice; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D015398:Signal Transduction; D014162:Transfection
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D019204:GTP-Binding Proteins