title: Serine phosphorylation regulates paxillin turnover during cell migration.
abstract: BACKGROUND
  Paxillin acts as an adaptor protein that localizes to focal adhesion. This protein is regulated during cell migration by phosphorylation on tyrosine, serine and threonine residues. Most of these phosphorylations have been implicated in the regulation of different steps of cell migration. The two major phosphorylation sites of paxillin in response to adhesion to an extracellular matrix are serines 188 and 190. However, the function of this phosphorylation event remains unknown. The purpose of this work was to determine the role of paxillin phosphorylation on residues S188 and S190 in the regulation of cell migration.
  
  
  RESULTS
  We used NBT-II epithelial cells that can be induced to migrate when plated on collagen. To examine the role of paxillin serines 188/190 in cell migration, we constructed an EGFP-tagged paxillin mutant in which S188/S190 were mutated into unphosphorylatable alanine residues. We provide evidence that paxillin is regulated by proteasomal degradation following polyubiquitylation of the protein. During active cell migration on collagen, paxillin is protected from proteasome-dependent degradation. We demonstrate that phosphorylation of serines 188/190 is necessary for the protective effect of collagen. In an effort to understand the physiological relevance of paxillin protection from degradation, we show that cells expressing the paxillin S188/190A interfering mutant spread less, have reduced protrusive activity but migrate more actively.
  
  
  CONCLUSIONS
  Our data demonstrate for the first time that serine-regulated degradation of paxillin plays a key role in the modulation of membrane dynamics and consequently, in the control of cell motility.
authors.affiliation: Institut Curie, CNRS UMR146, Centre Universitaire, Orsay, France. nancy.abouzeid@curie.u-psud.fr
authors.forename: Nancy
authors.initials: N
authors.lastname: Abou Zeid
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Vallés
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boyer