PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE - PubMed (original) (raw)
doi: 10.1038/ncb1675. Epub 2008 Jan 20.
Affiliations
- PMID: 18204440
- DOI: 10.1038/ncb1675
PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE
Sophie Pinner et al. Nat Cell Biol. 2008 Feb.
Erratum in
- Nat Cell Biol. 2008 Mar;10(3):370
Abstract
In three-dimensional matrices cancer cells move with a rounded, amoeboid morphology that is controlled by ROCK-dependent contraction of acto-myosin. In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo. Depletion of PDK1 alters the localization of ROCK1 and reduces its ability to drive cortical acto-myosin contraction. This form of ROCK1 regulation does not require PDK1 kinase activity, but instead involves direct binding of PDK1 to ROCK1 at the plasma membrane; PDK1 competes directly with RhoE for binding to ROCK1. In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility. This work uncovers a novel non-catalytic role for PDK1 in regulating cortical acto-myosin and cell motility.
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