Tau impacts on growth-factor-stimulated actin remodeling.
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.
Sharma
Vandana M
VM
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Litersky
Joel M
JM
Bhaskar
Kiran
K
Lee
Gloria
G
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D000199:Actins; D010982:Platelet-Derived Growth Factor; D014404:Tubulin; D016875:tau Proteins; D019061:src-Family Kinases