Role for Fes/Fps tyrosine kinase in microtubule nucleation through is Fes/CIP4 homology domain

J Biol Chem. 2003 Dec 5;278(49):49129-33. doi: 10.1074/jbc.C300289200. Epub 2003 Oct 8.

Abstract

We have previously demonstrated that Fes/Fps (Fes) tyrosine kinase is involved in Semaphorin3A-mediated signaling. Here we report a role for Fes tyrosine kinase in microtubule dynamics. A fibrous formation of Fes was observed in a kinase-dependent manner, which associated with microtubules and functionally correlated with microtubule bundling. Microtubule regeneration assays revealed that Fes aggregates colocalized with gamma-tubulin at microtubule nucleation sites in a Fes/CIP4 homology (FCH) domain-dependent manner and that expression of FCH domain-deleted Fes mutants blocked normal centrosome formation. In support of these observations, mouse embryonic fibroblasts derived from Fes-deficient mice displayed an aberrant structure of nucleation and centrosome with unbundling and disoriented filaments of microtubules. Our findings suggest that Fes plays a critical role in microtubule dynamics including microtubule nucleation and bundling through its FCH domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • DNA Primers
  • Fusion Proteins, gag-onc / physiology*
  • Mice
  • Microscopy, Immunoelectron
  • Microtubules / physiology*
  • Mutagenesis, Site-Directed
  • Protein-Tyrosine Kinases / physiology*

Substances

  • DNA Primers
  • Fusion Proteins, gag-onc
  • Protein-Tyrosine Kinases
  • v-fps oncogene protein, Fujinami sarcoma virus