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Tau impacts on growth-factor-stimulated actin remodeling
Journal article   Open access   Peer reviewed

Tau impacts on growth-factor-stimulated actin remodeling

Vandana M Sharma, Joel M Litersky, Kiran Bhaskar and Gloria Lee
Journal of cell science, Vol.120(Pt 5), pp.748-757
03/01/2007
DOI: 10.1242/jcs.03378
PMID: 17284520
url
https://doi.org/10.1242/jcs.03378View
Published (Version of record) Open Access

Abstract

The microtubule-associated protein tau interacts with the SH3 domain of non-receptor Src family protein tyrosine kinases. A potential consequence of the SH3 interaction is the upregulation of tyrosine kinase activity. Here we investigated the activation of Src or Fyn by tau, both in vitro and in vivo. Tau increased the kinase activity in in vitro assays and in transfected COS7 cells. In platelet-derived growth factor (PDGF)-stimulated fibroblasts, tau appeared to prime Src for activation following PDGF stimulation, as reflected by changes in Src-mediated actin rearrangements. In addition, while fibroblasts normally recovered actin stress fibers by 5-7 hours after PDGF stimulation, tau-expressing cells showed sustained actin breakdown. Microtubule association by tau was not required for the observed changes in actin morphology. Inhibition of Src kinases or a mutant deficient in Src interaction reduced the effects, implicating Src family protein tyrosine kinases as a mediator of the effects of tau on actin rearrangements. Our results provide evidence that the interaction of tau with Src upregulates tyrosine kinase activity and that this interaction allows tau to impact on growth-factor-induced actin remodeling.
Humans Actins - metabolism Cercopithecus aethiops tau Proteins - metabolism Platelet-Derived Growth Factor - pharmacology Gene Expression Regulation - drug effects Tubulin - metabolism Animals Transfection tau Proteins - genetics tau Proteins - physiology Fluorescent Antibody Technique src-Family Kinases - metabolism Cytoskeleton - metabolism Mice Phosphorylation - drug effects COS Cells 3T3 Cells Cytoskeleton - drug effects

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