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

Mutants of basic fibroblast growth factor identify different cellular response programs

W P Leenders1, V W van Hinsbergh, S T van Genesen

  • 1Department of Molecular Biology and Cell Biology, University of Nijmegen, The Netherlands.

Growth Factors (Chur, Switzerland)
|January 1, 1997
PubMed
Summary

Mutations in basic fibroblast growth factor (bFGF) impact its ability to stimulate cell division and tissue-specific responses. Intracellular routing modifications affect bFGF

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

Cleavage of bacteriophage M13 DNA by Haemophilus influenzae endonuclease-R.

Molecular biology reports·2013
Same author

Lens cell targetting for gene therapy of prevention of posterior capsule opacification.

Gene therapy·2006
Same author

The effect of alphaB-crystallin and Hsp27 on the availability of translation initiation factors in heat-shocked cells.

Cellular and molecular life sciences : CMLS·2006
Same author

Prevention of posterior capsule opacification by the induction of therapeutic apoptosis of residual lens cells.

Gene therapy·2005
Same author

Clubbed fingers: the claws we lost?

Medical hypotheses·2004
Same author

Influence of fibrin structure on the formation and maintenance of capillary-like tubules by human microvascular endothelial cells.

Angiogenesis·2003

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Basic fibroblast growth factor (bFGF) is a key signaling protein involved in cell growth, differentiation, and tissue repair.
  • Understanding the role of intracellular routing in bFGF function is crucial for elucidating its biological activities.
  • Mutations affecting bFGF's localization can alter its interactions with cellular targets and downstream signaling pathways.

Purpose of the Study:

  • To investigate the impact of mutations altering intracellular routing on basic fibroblast growth factor (bFGF) activity.
  • To assess the effects of these mutations on mitotic activity and tissue-specific responses in human umbilical vein endothelial cells (HUVECs) and rat lens epithelial cells.
  • To determine how modifications in nuclear localization sequences (NLS) and amino acid deletions influence bFGF's receptor binding and biological functions.

Related Experiment Videos

Main Methods:

  • Introduction of mutations into basic fibroblast growth factor (bFGF), including additional nuclear localization sequences (NLS) and amino acid deletions (26-29).
  • Assay of mutant bFGF proteins for mitotic activity (3H-thymidine incorporation) in HUVECs and rat lens epithelial cells.
  • Evaluation of bFGF-induced tissue-specific responses, such as urokinase plasminogen activator receptor (u-PAR) induction in HUVECs and fibre cell differentiation in rat lens epithelial cells.
  • Analysis of bFGF mutant receptor binding capacity.

Main Results:

  • Mutations affecting intracellular routing, particularly deletions of amino acids 26-29, impaired bFGF's ability to induce mitosis and u-PAR in HUVECs.
  • The delta 26-29 mutants exhibited reduced receptor binding, interacting with only a subset of receptors.
  • Addition of NLS to bFGF significantly inhibited fibre cell differentiation while having minimal impact on DNA synthesis stimulation.
  • The 17 kDa bFGF isoform with a delta 26-29 mutation showed wild-type differentiation activity but was a poor mitogen.

Conclusions:

  • Intracellular routing significantly influences the diverse biological activities of basic fibroblast growth factor (bFGF).
  • Specific mutations can differentially affect bFGF's mitogenic, receptor binding, and differentiation-inducing capabilities.
  • Targeting bFGF's localization pathways offers potential for modulating its specific cellular responses in therapeutic contexts.