Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility

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...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2001-06, Vol.20 (11), p.2723-2741
Main 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.
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Breast Neoplasms
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cell Movement - drug effects
Cell Movement - physiology
Chromones - pharmacology
Cytoskeletal Proteins
Enzyme Inhibitors - pharmacology
ERM
Female
FLIM
Green Fluorescent Proteins
Humans
Integrin beta1 - physiology
Isoenzymes - metabolism
Kinetics
Luminescent Proteins - analysis
Luminescent Proteins - genetics
Microscopy, Confocal
migration
Morpholines - pharmacology
Mutagenesis, Site-Directed
Phorbol 12,13-Dibutyrate - pharmacology
Phosphatidylinositol 3-Kinases - metabolism
Phosphoproteins - chemistry
Phosphoproteins - metabolism
Phosphorylation
Phosphothreonine - metabolism
PKC
Protein Kinase C - metabolism
Protein Kinase C-alpha
Recombinant Fusion Proteins - analysis
Recombinant Fusion Proteins - biosynthesis
Recombinant Fusion Proteins - chemistry
Tumor Cells, Cultured
wound
Wound Healing - physiology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/20.11.2723