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Epidermal growth factor-induced contraction regulates paxillin phosphorylation to temporally separate traction generation from de-adhesion
Molecular Biology of the Cell
  • Ian C. Schneider, Iowa State University
  • Cristen K. Hays, The Scripps Research Institute
  • Clare M. Waterman, National Institutes of Health
Document Type
Article
Publication Version
Published Version
Publication Date
7-1-2009
DOI
10.1091/mbc.E09-03-0219
Abstract

Directed cell migration is mediated by cycles of protrusion, adhesion, traction generation on the extracellular matrix and retraction. However, how the events after protrusion are timed, and what dictates their temporal order is completely unknown. We used acute epidermal growth factor (EGF) stimulation of epidermal keratinocytes to initiate the cell migration cycle to study the mechanism of the timing of adhesion, traction generation, and de-adhesion. Using microscopic and biochemical assays, we surprisingly found that at ∼2 min after EGF stimulation protrusion, activation of myosin-II, traction generation, adhesion assembly, and paxillin phosphorylation occurred nearly simultaneously, followed by a 10-min delay during which paxillin became dephosphorylated before cell retraction. Inhibition of myosin-II blocked both the EGF-stimulated paxillin phosphorylation and cell retraction, and a paxillin phosphomimic blocked retraction. These results suggest that EGF-mediated activation of myosin-II acts as a mechanical signal to promote a cycle of paxillin phosphorylation/dephosphorylation that mediates a cycle of adhesion strengthening and weakening that delays cell retraction. Thus, we reveal for the first time a mechanism by which cells may temporally segregate protrusion, adhesion, and traction generation from retraction during EGF-stimulated cell migration.

Comments

This is an article from Molecular Biology of the Cell 20 (2009): 3155, doi: 10.1091/mbc.E09-03-0219. Posted with permission.

Copyright Owner
The American Society for Cell Biology
Language
en
Date Available
2015-03-03
File Format
application/pdf
Citation Information
Ian C. Schneider, Cristen K. Hays and Clare M. Waterman. "Epidermal growth factor-induced contraction regulates paxillin phosphorylation to temporally separate traction generation from de-adhesion" Molecular Biology of the Cell Vol. 20 Iss. 13 (2009) p. 3155 - 3167
Available at: http://works.bepress.com/ian_schneider/2/