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

Src regulated by C-terminal phosphorylation is monomeric

A Weijland1, J C Williams, G Neubauer

  • 1European Molecular Biology Laboratory, Heidelberg, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|April 15, 1997
PubMed
Summary

The activity of c-Src protein tyrosine kinase is regulated by phosphorylation at Tyr-527. This study found that regulated Src exists as a monomer, indicating intramolecular structural changes control its enzymatic activity.

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

Salmonella Enteritidis phage type 21 outbreak in Austria, 2005.

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin·2017
Same author

Nilotinib-induced vasculopathy: identification of vascular endothelial cells as a primary target site.

Leukemia·2017
Same author

NDEL1-PDGFRB fusion gene in a myeloid malignancy with eosinophilia associated with resistance to tyrosine kinase inhibitors.

Leukemia·2016
Same author

Price Negotiation For Pharmaceuticals in Germany: High Influence Of Eu Price Weighting Method.

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research·2016
Same author

Overcoming MITF-conferred drug resistance through dual AURKA/MAPK targeting in human melanoma cells.

Cell death & disease·2016
Same author

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth.

Leukemia·2015

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • c-Src protein tyrosine kinase activity is regulated by C-terminal phosphorylation at Tyr-527.
  • Phosphorylation of Tyr-527 leads to reduced Src enzymatic activity by promoting tail-SH2 domain association.

Purpose of the Study:

  • To determine if Src regulation by C-terminal phosphorylation involves changes in quaternary structure or occurs within a monomeric form.
  • To investigate the structural basis of Src enzyme regulation.

Main Methods:

  • Purification of chicken Src lacking the unique domain from engineered Schizosaccharomyces pombe cells expressing Src and Csk.
  • Mass spectrometry to confirm homogeneous Tyr-527 phosphorylation.
  • Biophysical techniques including gel filtration chromatography, dynamic light scattering, and ultracentrifugation.

Related Experiment Videos

  • X-ray crystallography to determine the structure of regulated Src.

    • Main Results:

    • Purified Src was homogeneously phosphorylated at Tyr-527 and exhibited regulated enzymatic activity.
    • Biophysical analyses consistently indicated that the regulated form of Src is monomeric.
    • Crystallographic data confirmed the monomeric state with one molecule per asymmetric unit.
    • Structural rearrangements in regulated Src are intramolecular.

    Conclusions:

    • Src enzyme regulation by C-terminal phosphorylation occurs within a monomeric state.
    • The findings reveal that intramolecular structural changes underlie the regulation of c-Src activity.