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Science 14 October 1994:
Vol. 266. no. 5183, pp. 285 - 288
DOI: 10.1126/science.7939666
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Articles

Science, Vol 266, Issue 5183, 285-288
Copyright © 1994 by American Association for the Advancement of Science

articles

Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1

H Sun, NK Tonks, and D Bar-Sagi

Cold Spring Harbor Laboratory, NY 11724-2208.

Mitogen-activated protein kinases (MAP kinases) are common components of signaling pathways induced by diverse growth stimuli. Although the guanidine nucleotide-binding Ras proteins are known to be upstream activators of MAP kinases, the extent to which MAP kinases directly contribute to the mitogenic effect of Ras is as yet undefined. In this study, inhibition of MAP kinases by the MAP kinase phosphatase MKP-1 blocked the induction of DNA synthesis in quiescent rat embryonic fibroblast REF-52 cells by an activated mutant of Ras, V12Ras. These results suggest an essential role for activation of MAP kinases in the transition from the quiescent to the DNA replication phase of the eukaryotic cell cycle.


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