Article abstract
Nature Cell Biology 10, 127 - 137 (2008)
Published online: 20 January 2008 | doi:10.1038/ncb1675
There is an Erratum (March 2008) associated with this Article.
PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE
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.
- Tumour Cell Biology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
Correspondence to: Erik Sahai1 e-mail: Erik.Sahai@cancer.org.uk
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Apoptosis: caspases orchestrate the ROCK `n' blebNature Cell Biology News and Views (01 Apr 2001)
New dimensions in cell migrationNature Cell Biology News and Views (01 Aug 2003)
See all 4 matches for News And ViewsRESEARCH
Essential role of Id2 in negative regulation of IgE class switchingNature Immunology Article (01 Jan 2003)
Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motilityNature Cell Biology Article (01 Jan 2009)
See all 49 matches for Research
