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| Subject Categories: Membranes & Transport | Cell & Tissue Architecture |
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| The EMBO Journal
(2004) 23, 2531–2543, doi:10.1038/sj.emboj.7600267 Published online 10 June 2004 |
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PKD1/PKC promotes  v 3 integrin recycling and delivery to nascent focal adhesions |
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| Alison J Woods, Dominic P White, Patrick T Caswell and Jim C Norman |
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Department of Biochemistry, University of Leicester, Leicester, UK To whom correspondence should be addressed Jim C Norman, Department of Biochemistry, University of Leicester, Adrian Building, University Road, Leicester LE1 7RH, UK. Tel.: +44 116 252 5250; Fax: +44 116 252 3369; E-mail: jcn2@le.ac.uk Received 9 January 2004; Accepted 13 May 2004; Published online 10 June 2004. |
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| Abstract |
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| To identify kinases that regulate integrin recycling, we have immunoprecipitated v3 integrin from NIH 3T3 fibroblasts in the presence and absence of primaquine (a drug that inhibits receptor recycling and leads to accumulation of integrins in endosomes) and screened for co-precipitating kinases. Primaquine strongly promoted association of v3 integrin with PKD1, and fluorescence microscopy indicated that integrin and PKD1 associate at a vesicular compartment that is downstream of a Rab4-dependent transport step. PKD1 association was mediated by the C-terminal region of the 3 integrin cytodomain, and mutants of 3 that were unable to recruit PKD1 did not recycle in a PDGF-dependent fashion. Furthermore, suppression of endogenous PKD1 levels by RNAi, or overexpression of catalytically inactive PKD1 inhibited PDGF-dependent recycling of v3 from early endosomes to the plasma membrane and blocked recruitment of v3 to newly formed focal adhesions during cell spreading. These data indicate that PKD1 influences cell migration by directing vesicular transport of the v3 integrin heterodimer. |
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| Keywords: focal adhesion, integrin, PKD1, Rab4, recycling |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHIncreased CCR4 Expression in Cutaneous T Cell Lymphoma Journal of Investigative Dermatology Original Article PKCε controls the traffic of β1 integrins in motile cells The EMBO Journal Article (15 Jul 2002) PKCϵ-mediated phosphorylation of vimentin controls integrin recycling and motility The EMBO Journal Article (16 Nov 2005) Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts Nature Cell Biology Article (01 Dec 2007) Spatial and temporal regulation of protein kinase D (PKD) The EMBO Journal Article (15 Jun 2000) |
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