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

erbB-2 autophosphorylation is required for mitogenic action and high-affinity substrate coupling.

O Segatto1, F Lonardo, K Helin

  • 1Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Oncogene
|July 1, 1992
PubMed
Summary

Autophosphorylation of erbB-2 (a receptor tyrosine kinase) is crucial for its mitogenic signaling in normal cells. This process enhances the kinase's affinity for substrates like phospholipase C-gamma (PLC-gamma).

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

Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis.

Nature communications·2024
Same author

Correction: A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation.

Oncogene·2024
Same author

Correction for Querbes et al., "A JC Virus-Induced Signal Is Required for Infection of Glial Cells by a Clathrin- and eps15-Dependent Pathway".

Journal of virology·2024
Same author

CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.

Nature communications·2022
Same author

Say-Barber-Biesecker-Young-Simpson syndrome and Genitopatellar syndrome: Lumping or splitting?

Clinical genetics·2017
Same author

Diagnostic application of a capture based NGS test for the concurrent detection of variants in sequence and copy number as well as LOH.

Clinical genetics·2017

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • Autophosphorylation of gp185erbB-2 is essential for transforming activity in overexpression scenarios.
  • The role and biochemical basis of erbB-2 autophosphorylation in normal cell mitogenic signaling remain unclear.

Purpose of the Study:

  • To investigate the extent to which autophosphorylation regulates erbB-2 mitogenic signaling in normal cells.
  • To elucidate the biochemical mechanism underlying autophosphorylation's regulatory function in erbB-2 signaling.

Main Methods:

  • Utilized a chimeric molecule: epidermal growth factor receptor (EGFR) extracellular domain fused to erbB-2 transmembrane and intracellular domains.
  • Created an EGFR/erbB-2 mutant (EGFR/erbB-2 5P) with multiple tyrosine-to-phenylalanine substitutions at autophosphorylation sites.

Related Experiment Videos

  • Assessed chimera activity in NR6 cells upon epidermal growth factor (EGF) stimulation, measuring phosphotyrosine content, mitogenic signaling, and phospholipase C-gamma (PLC-gamma) interaction.

    • Main Results:

    • The EGFR/erbB-2 5P mutant showed significantly reduced phosphotyrosine levels post-EGF stimulation compared to the wild-type chimera.
    • The 5P mutant exhibited impaired mitogenic signaling at physiological EGF levels.
    • While the 5P mutant could phosphorylate PLC-gamma, it demonstrated decreased affinity and failed co-immunoprecipitation, indicating reduced substrate interaction.

    Conclusions:

    • Autophosphorylation significantly enhances the affinity of the erbB-2 kinase for its cellular substrates.
    • Under physiological conditions, erbB-2 autophosphorylation is indispensable for effective mitogenic signaling.
    • This finding clarifies the critical role of erbB-2 autophosphorylation in normal cellular processes.