%0 Journal Article
%T Serine phosphorylation regulates paxillin turnover during cell migration
%A Nancy Abou Zeid
%A Ana-Maria Vall¨¦s
%A Brigitte Boyer
%J Cell Communication and Signaling
%D 2006
%I BioMed Central
%R 10.1186/1478-811x-4-8
%X 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.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.Cell migration is a cyclic multistep event that involves cell polarization and extension of membrane protrusions at the leading edge. At the front of the protrusion, cell-substratum adhesive complexes are formed providing traction points for translocation. Adhesive complexes at the cell rear are then released as the cell continues to move forward [1].Integrins are cell-surface adhesion receptors that link the extracellular matrix (ECM) to the intracellular actin cytoskeleton [2]. Integrins are heterodimeric receptors that interact with numerous structural and signaling molecules to form large protein complexes, the focal adhesions. Upon binding to ECM elements, integrins cluster and interact with an array of structural and signaling molecules to form large protein complexes, the focal adhesions. These structures are spatially regulated during cell migration as they assemble at the leading edge to stabilize new membrane protrusions and disassemble at
%U http://www.biosignaling.com/content/4/1/8