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

The Grb2-mSos1 complex binds phosphopeptides with higher affinity than Grb2

Y M Chook1, G D Gish, C M Kay

  • 1Department of Biochemistry, University of Toronto, Ontario, Canada.

The Journal of Biological Chemistry
|November 29, 1996
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

Serial femtosecond and serial synchrotron crystallography can yield data of equivalent quality: A systematic comparison.

Science advances·2021
Same author

Fixed target matrix for femtosecond time-resolved and in situ serial micro-crystallography.

Structural dynamics (Melville, N.Y.)·2016
Same author

Iron-mineral accretion from acid mine drainage and its application in passive treatment.

Environmental technology·2015
Same author

Structural factors underlying the species barrier and susceptibility to infection in prion disease.

Biochemistry and cell biology = Biochimie et biologie cellulaire·2010
Same author

Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential.

Mini reviews in medicinal chemistry·2008
Same author

Structural and functional analysis of a truncated form of Saccharomyces cerevisiae ATP sulfurylase: C-terminal domain essential for oligomer formation but not for activity.

Protein engineering·2004

Epidermal growth factor (EGF) signaling involves complexes like EGFR-Grb2-mSos1. The Grb2-mSos1 complex enhances binding to phosphopeptides, suggesting linked SH2 and SH3 domains.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Epidermal growth factor (EGF) binding activates the epidermal growth factor receptor (EGFR), initiating downstream signaling pathways.
  • Key signaling proteins involved include Grb2 and mSos1, which form complexes with EGFR and Shc to activate the Ras GTPase.

Purpose of the Study:

  • To investigate the binding affinities of Grb2, mSos1, and their complex with phosphotyrosine-containing peptides.
  • To elucidate the role of the Grb2-mSos1 complex in mediating interactions within EGF signaling pathways.

Main Methods:

  • Purification of Grb2, mSos1, and the Grb2-mSos1 complex to high homogeneity.
  • Determination of binding affinities (KD) using phosphotyrosine-containing peptides derived from EGFR and Shc.
  • Stoichiometry analysis of the Grb2-mSos1 complex.

Related Experiment Videos

Main Results:

  • mSos1 binds Grb2 with a dissociation constant (KD) of 0.4 microM, forming a 1:1 complex.
  • Grb2 alone binds EGFR- and Shc-derived phosphopeptides with KDs of 0.7 microM and 0.2 microM, respectively.
  • The Grb2-mSos1 complex exhibits enhanced binding affinities for EGFR- and Shc-derived phosphopeptides (KD of 0.3 microM and 31 nM, respectively) compared to Grb2 alone.

Conclusions:

  • The presence of mSos1 in the Grb2-mSos1 complex influences the binding of the Grb2 SH2 domain to phosphopeptides.
  • These findings suggest that the SH2 and SH3 domains of Grb2 may not function independently within the Grb2-mSos1 complex, potentially being indirectly linked by mSos1.