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Updated: Aug 19, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
The unique N-terminus of R-ras is required for Rac activation and precise regulation of cell migration
Stephen P Holly1, Mark K Larson, Leslie V Parise
1Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Abstract:
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 beta3 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.
Insights
The unique N-terminus of R-Ras protein positively regulates Rac activation and cell spreading but negatively impacts cell migration. This finding clarifies R-Ras
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Ras family GTPases, including R-Ras, regulate crucial integrin-dependent cellular functions like adhesion, spreading, and migration.
- Oncogenic Ras GTPases and R-Ras share sequence homology but induce distinct cellular behaviors, suggesting unique regulatory mechanisms.
Purpose of the Study:
- To investigate the structural basis for R-Ras-specific signaling.
- To determine if the unique N-terminal 26 amino acid extension of R-Ras is responsible for its distinct cellular functions.
Main Methods:
- Utilized a 32D mouse myeloid cell line.
- Compared the signaling activities of full-length R-Ras and a truncated version lacking the N-terminal 26 amino acids.
Main Results:
- Full-length R-Ras activated Rac, leading to cell spreading, while truncated R-Ras did not activate Rac and showed reduced spreading.
- Truncated R-Ras exhibited increased beta3 integrin-dependent cell migration compared to full-length R-Ras.
- Subcellular localization and cell adhesion were unaffected by the N-terminal extension.
Conclusions:
- The N-terminus of R-Ras positively regulates Rac activation and cell spreading.
- The N-terminus of R-Ras negatively regulates R-Ras-mediated cell migration.
- The N-terminal extension dictates specific R-Ras functions, differentiating its signaling pathways from other Ras GTPases.
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