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| Subject Categories: Cell & Tissue Architecture | Signal Transduction |
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| The EMBO Journal
(2008) 27, 1206–1218, doi:10.1038/emboj.2008.55 Published online 27 March 2008 |
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| G protein-coupled receptor kinase 2 positively regulates epithelial cell migration |
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| Petronila Penela1, Catalina Ribas1, Ivette Aymerich1, Niels Eijkelkamp2, Olga Barreiro3, Cobi J Heijnen2, Annemieke Kavelaars2, Francisco Sánchez-Madrid3 and Federico Mayor Jr1 |
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1 Departamento de Biología Molecular and Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain 2 Laboratory of Psychoneuroimmunology, University Medical Center, Utrecht, The Netherlands 3 Servicio de Inmunología, Hospital Universitario La Princesa, Madrid, Spain To whom correspondence should be addressed Petronila Penela, Departamento de Biología Molecular y Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma Madrid, Universidad Autónoma de Madrid, Madrid, Madrid 28049, Spain. Tel.: +34 91 196 4626; Fax: +34 91 196 4420; E-mail: ppenela@cbm.uam.es Federico Mayor Jr, Departamento de Biología Molecular y Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma Madrid, Universidad Autónoma de Madrid, Madrid, Madrid 28049, Spain. Tel.: +34 91 196 4626; Fax: +34 91 196 4420; E-mail: fmayor@cbm.uam.es Received 28 August 2007; Accepted 27 February 2008; Published online 27 March 2008. |
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| Abstract |
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| Cell migration requires integration of signals arising from both the extracellular matrix and messengers acting through G protein-coupled receptors (GPCRs). We find that increased levels of G protein-coupled receptor kinase 2 (GRK2), a key player in GPCR regulation, potentiate migration of epithelial cells towards fibronectin, whereas such process is decreased in embryonic fibroblasts from hemizygous GRK2 mice or upon knockdown of GRK2 expression. Interestingly, the GRK2 effect on fibronectin-mediated cell migration involves the paracrine/autocrine activation of a sphingosine-1-phosphate (S1P) Gi-coupled GPCR. GRK2 positively modulates the activity of the Rac/PAK/MEK/ERK pathway in response to adhesion and S1P by a mechanism involving the phosphorylation-dependent, dynamic interaction of GRK2 with GIT1, a key scaffolding protein in cell migration processes. Furthermore, decreased GRK2 levels in hemizygous mice result in delayed wound healing rate in vivo, consistent with a physiological role of GRK2 as a regulator of coordinated integrin and GPCR-directed epithelial cell migration. |
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| Keywords: GIT1, GRK2, integrins, MAPK, migration |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSCell polarization mechanisms during directed cell migration Nature Cell Biology News and Views (01 Apr 2005) RESEARCHG protein-coupled receptor kinase 2 positively regulates epithelial cell migration The EMBO Journal Article CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility The EMBO Journal Article CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility The EMBO Journal Article (15 Nov 2006) |
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