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- Title
Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility.
- Authors
Ng, Tony; Parsons, Maddy; Hughes, William E.; Monypenny, James; Zicha, Daniel; Gautreau, Alexis; Arpin, Monique; Gschmeissner, Steve; Verveer, Peter J.; Bastiaens, Philippe I.H.; Parker, Peter J.
- Abstract
Protein kinase C (PKC) α has been implicated in β1 integrin-mediated cell migration. Stable expression of PKCα is shown here to enhance wound closure. This PKC-driven migratory response directly correlates with increased C-terminal threonine phosphorylation of ezrin/moesin/radixin (ERM) at the wound edge. Both the wound migratory response and ERM phosphorylation are dependent upon the catalytic function of PKC and are susceptible to inhibition by phosphatidylinositol 3-kinase blockade. Upon phorbol 12,13-dibutyrate stimulation, green fluorescent protein-PKCα and β1 integrins co-sediment with ERM proteins in low-density sucrose gradient fractions that are enriched in transferrin receptors. Using fluorescence lifetime imaging microscopy, PKCα is shown to form a molecular complex with ezrin, and the PKC-co-precipitated endogenous ERM is hyperphosphorylated at the C-terminal threonine residue, i.e. activated. Electron microscopy showed an enrichment of both proteins in plasma membrane protrusions. Finally, overexpression of the C-terminal threonine phosphorylation site mutant of ezrin has a dominant inhibitory effect on PKCα-induced cell migration. We provide the first evidence that PKCα or a PKCα-associated serine/threonine kinase can phosphorylate the ERM C-terminal threonine residue within a kinase-ezrin molecular complex in vivo.
- Subjects
INTEGRINS; GLYCOPROTEINS; CELL adhesion molecules; CELL motility; PROTEIN kinases; PHOSPHORYLATION
- Publication
EMBO Journal, 2001, Vol 20, Issue 11, p2723
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/20.11.2723