Stimulation of Membrane Ruffling and MAP Kinase Activation by Distinct Effectors of RAS
- 9 February 1996
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 271 (5250) , 810-812
- https://doi.org/10.1126/science.271.5250.810
Abstract
The RAS guanine nucleotide binding proteins activate multiple signaling events that regulate cell growth and differentiation. In quiescent fibroblasts, ectopic expression of activated H-RAS (H-RASV12, where V12 indicates valine-12) induces membrane ruffling, mitogen-activated protein (MAP) kinase activation, and stimulation of DNA synthesis. A mutant of activated H-RAS, H-RASV12C40 (where C40 indicates cysteine-40), was identified that was defective for MAP kinase activation and stimulation of DNA synthesis, but retained the ability to induce membrane ruffling. Another mutant of activated H-RAS, H-RASV12S35 (where S35 indicates serine-35), which activates MAP kinase, was defective for stimulation of membrane ruffling and induction of DNA synthesis. Expression of both mutants resulted in a stimulation of DNA synthesis that was comparable to that induced by H-RASV12. These results indicate that membrane ruffling and activation of MAP kinase represent distinct RAS effector pathways and that input from both pathways is required for the mitogenic activity of RAS.Keywords
This publication has 13 references indexed in Scilit:
- Selective activation of the JNK signaling cascadeand c-Jun transcriptional activity by the small GTPases Rac and Cdc42HsCell, 1995
- The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathwayCell, 1995
- Multiple ras functions can contribute to mammalian cell transformationCell, 1995
- Inhibition of Ras-Induced DNA Synthesis by Expression of the Phosphatase MKP-1Science, 1994
- Transformation of Mammalian Cells by Constitutively Active MAP Kinase KinaseScience, 1994
- Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cellsCell, 1994
- The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domainCell, 1993
- The small GTP-binding protein rac regulates growth factor-induced membrane rufflingCell, 1992
- Distinct Protein Targets for Signals Acting at the c- fos Serum Response ElementScience, 1991
- Induction of Membrane Ruffling and Fluid-Phase Pinocytosis in Quiescent Fibroblasts by ras ProteinsScience, 1986