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| Subject Categories: Membranes & Transport | Signal Transduction |
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| The EMBO Journal
(2005) 24, 3834–3845, doi:10.1038/sj.emboj.7600847 Published online 3 November 2005 |
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PKC -mediated phosphorylation of vimentin controls integrin recycling and motility |
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| Johanna Ivaska1, Karoliina Vuoriluoto1, Tuomas Huovinen1, Ichiro Izawa2, Masaki Inagaki2 and Peter J Parker3 |
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1 VTT Technical Research Centre for Finland, Medical Biotechnology and University of Turku Centre for Biotechnology, Turku, Finland 2 Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Aichi, Japan 3 Protein Phosphorylation Laboratory, London Research Institute, London, UK To whom correspondence should be addressed Peter J Parker, Protein Phosphorylation Laboratory, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Tel.:+44 20 7269 3513; Fax: +44 20 7269 3094; E-mail: peter.parker@cancer.org.uk Received 29 June 2005; Accepted 28 September 2005; Published online 3 November 2005. |
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| Abstract |
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PKC controls the transport of endocytosed  1-integrins to the plasma membrane regulating directional cell motility. Vimentin, an intermediate filament protein upregulated upon epithelial cell transformation, is shown here to be a proximal PKC target within the recycling integrin compartment. On inhibition of PKC and vimentin phosphorylation, integrins become trapped in vesicles and directional cell motility towards matrix is severely attenuated. In vitro reconstitution assays showed that PKC dissociates from integrin containing endocytic vesicles in a selectively phosphorylated vimentin containing complex. Mutagenesis of PKC (controlled) sites on vimentin and ectopic expression of the variant leads to the accumulation of intracellular PKC/integrin positive vesicles. Finally, introduction of ectopic wild-type vimentin is shown to promote cell motility in a PKC-dependent manner; alanine substitutions in PKC (controlled) sites on vimentin abolishes the ability of vimentin to induce cell migration, whereas the substitution of these sites with acidic residues enables vimentin to rescue motility of PKC null cells. Our results indicate that PKC-mediated phosphorylation of vimentin is a key process in integrin traffic through the cell. |
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| Keywords: integrin, intermediate filament, migration, PKC, vimentin |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHCircumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer Nature Immunology Article (01 Oct 2001) Nature Immunology Article (01 Apr 2001) PKC controls HGF-dependent c-Met traffic, signalling and cell migration The EMBO Journal Article (29 Sep 2004) |
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