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 Waters, Seema Khurana

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)4807-4817
Number of pages11
JournalMolecular Biology of the Cell
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2004

Fingerprint

Cell Movement
Tyrosine
Phosphorylation
Actin Cytoskeleton
Microfilament Proteins
HeLa Cells
villin
src-Family Kinases
Phenylalanine
Glutamic Acid
Intercellular Signaling Peptides and Proteins
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Tomar, A., Wang, Y., Kumar, N., George, S., Ceacareanu, B., Hassid, A., ... Khurana, S. (2004). Regulation of cell motility by tyrosine phosphorylated villin. Molecular Biology of the Cell, 15(11), 4807-4817. https://doi.org/10.1091/mbc.E04-05-0431

Regulation of cell motility by tyrosine phosphorylated villin. / Tomar, Alok; Wang, Yaohong; Kumar, Narendra; George, Sudeep; Ceacareanu, Bogdan; Hassid, Aviv; Chapman, Kenneth E.; Aryal, Ashish M.; Waters, Christopher; Khurana, Seema.

In: Molecular Biology of the Cell, Vol. 15, No. 11, 01.11.2004, p. 4807-4817.

Research output: Contribution to journalArticle

Tomar, A, Wang, Y, Kumar, N, George, S, Ceacareanu, B, Hassid, A, Chapman, KE, Aryal, AM, Waters, C & Khurana, S 2004, 'Regulation of cell motility by tyrosine phosphorylated villin', Molecular Biology of the Cell, vol. 15, no. 11, pp. 4807-4817. https://doi.org/10.1091/mbc.E04-05-0431
Tomar A, Wang Y, Kumar N, George S, Ceacareanu B, Hassid A et al. Regulation of cell motility by tyrosine phosphorylated villin. Molecular Biology of the Cell. 2004 Nov 1;15(11):4807-4817. https://doi.org/10.1091/mbc.E04-05-0431
Tomar, Alok ; Wang, Yaohong ; Kumar, Narendra ; George, Sudeep ; Ceacareanu, Bogdan ; Hassid, Aviv ; Chapman, Kenneth E. ; Aryal, Ashish M. ; Waters, Christopher ; Khurana, Seema. / Regulation of cell motility by tyrosine phosphorylated villin. In: Molecular Biology of the Cell. 2004 ; Vol. 15, No. 11. pp. 4807-4817.
@article{7ccc3c5c37f647428f94f259c221c481,
title = "Regulation of cell motility by tyrosine phosphorylated villin",
abstract = "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.",
author = "Alok Tomar and Yaohong Wang and Narendra Kumar and Sudeep George and Bogdan Ceacareanu and Aviv Hassid and Chapman, {Kenneth E.} and Aryal, {Ashish M.} and Christopher Waters and Seema Khurana",
year = "2004",
month = "11",
day = "1",
doi = "10.1091/mbc.E04-05-0431",
language = "English (US)",
volume = "15",
pages = "4807--4817",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "11",

}

TY - JOUR

T1 - Regulation of cell motility by tyrosine phosphorylated villin

AU - Tomar, Alok

AU - Wang, Yaohong

AU - Kumar, Narendra

AU - George, Sudeep

AU - Ceacareanu, Bogdan

AU - Hassid, Aviv

AU - Chapman, Kenneth E.

AU - Aryal, Ashish M.

AU - Waters, Christopher

AU - Khurana, Seema

PY - 2004/11/1

Y1 - 2004/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=6344272215&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6344272215&partnerID=8YFLogxK

U2 - 10.1091/mbc.E04-05-0431

DO - 10.1091/mbc.E04-05-0431

M3 - Article

VL - 15

SP - 4807

EP - 4817

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 11

ER -