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Published February 18, 2000 | Published
Journal Article Open

Ras1 Promotes Cellular Growth in the Drosophila Wing

Abstract

The Ras GTPase links extracellular mitogens to intracellular mechanisms that control cell proliferation. To understand how Ras regulates proliferation in vivo, we activated or inactivated Ras in cell clones in the developing Drosophila wing. Cells lacking Ras were smaller, had reduced growth rates, accumulated in G1, and underwent apoptosis due to cell competition. Conversely, activation of Ras increased cell size and growth rates and promoted G1/S transitions. Ras upregulated the growth driver dMyc, and both Ras and dMyc increased levels of cyclin E posttranscriptionally. We propose that Ras primarily promotes growth and that growth is coupled to G1/S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit.

Additional Information

© 2000 Cell Press. Received 4 August 1999, Revised 11 January 2000, Available online 11 April 2001. We thank Celeste Berg, Peter Gallant, Felix Karim, and Denise Montell for fly stocks; Robert Eisenman, Peter Gallant, and Helena Richardson for antibodies; Aida de la Cruz, Mary Kay Dolejsi (grant #5P30CA15704–26), Adrian Quintanilla, and the Fred Hutchinson Cancer Research Center Flow Cytometry and Image Analysis facilities for technical assistance; and Jon Cooper, Tom Neufeld, and members of the Edgar lab for helpful advice, discussions, and comments on the manuscript. D. A. P. is a National Science Foundation predoctoral fellow, and B. A. E. is a Rita Allen Scholar. This work supported by the National Institutes of Health (GM51186).

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