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Mol Biol Cell. 2009 Jul;20(13):3155-67. doi: 10.1091/mbc.E09-03-0219. Epub 2009 Apr 29.

Epidermal growth factor-induced contraction regulates paxillin phosphorylation to temporally separate traction generation from de-adhesion.

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  • 1Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ians@iastate.edu

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 approximately 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.

PMID:
19403690
[PubMed - indexed for MEDLINE]
PMCID:
PMC2704165
Free PMC Article
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