Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Identification and characterization of mutations in Ha-Ras that selectively decrease binding to cRaf-1

D G Winkler1, J C Johnson, J A Cooper

  • 1Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

The Journal of Biological Chemistry
|September 26, 1997
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.

The Journal of biological chemistry·2001
Same author

Analyses of TC21/R-Ras2 signaling and biological activity.

Methods in enzymology·2001
Same author

Prenylated Rab acceptor protein is a receptor for prenylated small GTPases.

The Journal of biological chemistry·2001
Same author

Negative regulation of the serine/threonine kinase B-Raf by Akt.

The Journal of biological chemistry·2000
Same author

Src family kinases are required for integrin but not PDGFR signal transduction.

The EMBO journal·1999
Same author

Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study.

BMJ (Clinical research ed.)·1999
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
Same journal

Introduction to the Thematic Review Series on Intracellular Protein Degradation. The ubiquitous biology of intracellular protein degradation: a tribute to Alfred L. ("Fred") Goldberg.

The Journal of biological chemistry·2026
Same journal

Correction: Aromatic residue-rich amino-terminal segments of temporin L self-assemble into collagen-mimetic peptides with cell-adhesion properties.

The Journal of biological chemistry·2026
Same journal

YhbO is a DJ-1 family glyoxalase and α-oxoaldehyde hydratase that confers resistance to reactive carbonyl stress (112).

The Journal of biological chemistry·2026
Same journal

ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.

The Journal of biological chemistry·2026
Same journal

PAX8 controls proximal tubule epithelial identity and stress response through epigenetic modification of distal regulatory elements.

The Journal of biological chemistry·2026
See all related articles

Ras oncoprotein binding to effector proteins like Raf kinase is key for cell transformation. Mutants reveal Ras interactions outside the effector domain, linking Raf binding to MAP kinase activation and PI3 kinase activation as a primary Ras effect.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Signal transduction

Background:

  • The oncoprotein Ras drives cell transformation by interacting with effector proteins.
  • Ras effector binding is specific to its GTP-bound state and requires the Ras effector domain.
  • While Raf kinases are well-characterized Ras effectors, others like RalGDS and PI3 kinase are also implicated.

Purpose of the Study:

  • To elucidate the binding mechanism between cRaf-1 and Ras.
  • To investigate the roles of other Ras effector proteins in cellular transformation.
  • To characterize Ras mutants with altered cRaf-1 binding affinities.

Main Methods:

  • Isolation and characterization of activated Ras mutants.
  • Assessment of binding affinities to cRaf-1 and other candidate Ras effectors.

Related Experiment Videos

  • Analysis of fibroblast transformation, MAP kinase activation, and PI3 kinase activation.

    • Main Results:

    • Ras mutants with reduced cRaf-1 binding were generated.
    • Surface-exposed Ras residues outside the effector domain mediate differential interactions with effectors.
    • Fibroblast transformation correlated with cRaf-1 binding and MAP kinase activation.
    • PI3 kinase activation was observed independently of significant MAP kinase activation.

    Conclusions:

    • Ras interaction with cRaf-1 is crucial for MAP kinase pathway activation and fibroblast transformation.
    • PI3 kinase activation represents a distinct and potentially primary signaling output of Ras.
    • Ras utilizes distinct binding interfaces for different effector proteins, enabling pathway specificity.