Role for Fes/Fps tyrosine kinase in microtubule nucleation through is Fes/CIP4 homology domain.
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.
Takahashi
Shusuke
S
Department of Genome Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
Inatome
Ryoko
R
Hotta
Azusa
A
Qin
Qingyu
Q
Hackenmiller
Renee
R
Simon
M Celeste
MC
Yamamura
Hirohei
H
Yanagi
Shigeru
S
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D017931:DNA Primers; D015681:Fusion Proteins, gag-onc / Q000502:physiology*; D051379:Mice; D016253:Microscopy, Immunoelectron; D008870:Microtubules / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D011505:Protein-Tyrosine Kinases / Q000502:physiology*
D017931:DNA Primers; D015681:Fusion Proteins, gag-onc; D011505:Protein-Tyrosine Kinases; C068415:v-fps oncogene protein, Fujinami sarcoma virus