Related Experiment Video

Updated: Aug 30, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

C-terminal sequences in R-Ras are involved in integrin regulation and in plasma membrane microdomain distribution

Malene Hansen1, Ian A Prior, Paul E Hughes

  • 1Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. maha@itsa.ucsf.edu

Biochemical and Biophysical Research Communications
|November 19, 2003
PubMed

Insights

Small GTPases R-Ras and H-Ras have different effects on integrin activation. Specific C-terminal sequences in R-Ras are crucial for its ability to enhance integrin activation, independent of Nck binding.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Small GTPases, including R-Ras and H-Ras, are homologous proteins with distinct cellular functions.
  • These proteins differentially regulate integrin affinity, impacting cell adhesion and migration.
  • H-Ras typically suppresses integrin activation, while R-Ras can reverse this effect.

Purpose of the Study:

  • To identify specific protein sequences responsible for the divergent effects of R-Ras and H-Ras on integrin activation.
  • To investigate the role of the C-terminal hypervariable region of R-Ras in modulating integrin activity.
  • To explore the subcellular localization of R-Ras and H-Ras and its correlation with their function.

Main Methods:

  • Construction and analysis of H-Ras/R-Ras chimeras to map functional domains.
  • Assays to measure integrin activation in response to chimeric protein expression.
  • Subcellular localization studies comparing activated H-Ras and R-Ras in lipid rafts.

Main Results:

  • Sequences within the R-Ras C-terminal hypervariable region (amino acids 175-203) are essential for R-Ras-mediated enhancement of integrin activation in CHO cells.
  • A proline-rich Nck-binding site within this region was not critical for the integrin activation phenotype.
  • The GTPase TC21 exhibited R-Ras-like behavior regarding integrin activation.
  • Activated R-Ras remained localized in lipid rafts, unlike H-Ras which dissociates upon activation.
  • Chimeric proteins localized to lipid rafts regardless of their integrin phenotype, suggesting localization is separable from functional effects.

Conclusions:

  • The C-terminal region of R-Ras, specifically amino acids 175-203, dictates its ability to promote integrin activation.
  • Subcellular localization in lipid rafts is a key feature of R-Ras function, distinguishing it from H-Ras.
  • Integrin activation and lipid raft localization are distinct but related functions influenced by R-Ras C-terminal sequences.

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