Regulation of cell motility by tyrosine phosphorylated villin

Alok Tomar, Yaohong Wang, Narendra Kumar, Sudeep George, Bogdan Ceacareanu, Aviv Hassid, Kenneth E. Chapman, Ashish M. Aryal, Christopher M. Waters, Seema Khurana

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Temporal and spatial regulation of the actin cytoskeleton is vital for cell migration. Here, we show that an epithelial cell actin-binding protein, villin, plays a crucial role in this process. Overexpression of villin in doxycyline-regulated HeLa cells enhanced cell migration. Villin-induced cell migration was modestly augmented by growth factors. In contrast, tyrosine phosphorylation of villin and villin-induced cell migration was significantly inhibited by the src kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine (PP2) as well as by Overexpression of a dominant negative mutant of c-src. These data suggest that phosphorylation of villin by c-src is involved in the actin cytoskeleton remodeling necessary for cell migration. We have previously shown that villin is tyrosine phosphorylated at four major sites. To further investigate the role of tyrosine phosphorylated villin in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) in HeLa cells. We determined that tyrosine phosphorylation at residues 60, 81, and 256 of human villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton. Collectively, these studies define how biophysical events such as cell migration are actuated by biochemical signaling pathways involving tyrosine phosphorylation of actin binding proteins, in this case villin.

Original languageEnglish
Pages (from-to)4807-4817
Number of pages11
JournalMolecular Biology of the Cell
Issue number11
StatePublished - Nov 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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