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A more recent version of this article appeared on May 1, 2005
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Submitted on December 22, 2003
Accepted on March 1, 2005
*Department of Pharmacology, Lineberger Comprehensive Cancer Center, and Carolina Cardiovascular Biology Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
Monitoring Editor: Mark Ginsberg
The Ras family GTPase, R-Ras, elicits important integrin-dependent cellular behaviors such as adhesion, spreading and migration. While oncogenic Ras GTPases and R-Ras share extensive sequence homology, R-Ras induces a distinct set of cellular behaviors. To explore the structural basis for these differences, we asked whether the unique N-terminal 26 amino acid extension of R-Ras was responsible for R-Ras-specific signaling events. Using a 32D mouse myeloid cell line, we show that full-length R-Ras activates Rac and induces Rac-dependent cell spreading. In contrast, truncated R-Ras lacking its first 26 amino acids fails to activate Rac, resulting in reduced cell spreading. Truncated R-Ras also stimulates more 
3 integrin-dependent cell migration than full-length R-Ras, suggesting that the N-terminus may negatively regulate cell movement. However, neither the subcellular localization of R-Ras nor its effects on cell adhesion are affected by the presence or absence of the N-terminus. These results indicate that the N-terminus of R-Ras positively regulates specific R-Ras functions such as Rac activation and cell spreading but negatively regulates R-Ras-mediated cell migration.
Present address: Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Address correspondence to:
Leslie V. Parise (parise{at}med.unc.edu)
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