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PAK4 Kinase Activity Plays a Crucial Role in the Podosome Ring of Myeloid Cells.
Foxall, Elizabeth; Staszowska, Adela; Hirvonen, Liisa M; Georgouli, Mirella; Ciccioli, Mariacristina; Rimmer, Alexander; Williams, Lynn; Calle, Yolanda; Sanz-Moreno, Victoria; Cox, Susan; Jones, Gareth E; Wells, Claire M.
Afiliación
  • Foxall E; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK.
  • Staszowska A; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK.
  • Hirvonen LM; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK.
  • Georgouli M; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK.
  • Ciccioli M; Department of Life Sciences, University of Roehampton, London, UK.
  • Rimmer A; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
  • Williams L; Kennedy Institute of Rheumatology, Oxford University, Oxford, UK.
  • Calle Y; Department of Life Sciences, University of Roehampton, London, UK.
  • Sanz-Moreno V; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK; Barts Cancer Institute, Queen Mary University of London, London, UK.
  • Cox S; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK.
  • Jones GE; Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK. Electronic address: gareth.jones@kcl.ac.uk.
  • Wells CM; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK. Electronic address: claire.wells@kcl.ac.uk.
Cell Rep ; 29(11): 3385-3393.e6, 2019 12 10.
Article en En | MEDLINE | ID: mdl-31825823
p21-Activated kinase 4 (PAK4), a serine/threonine kinase, is purported to localize to podosomes: transient adhesive structures that degrade the extracellular matrix to facilitate rapid myeloid cell migration. We find that treatment of transforming growth factor ß (TGF-ß)-differentiated monocytic (THP-1) cells with a PAK4-targeted inhibitor significantly reduces podosome formation and induces the formation of focal adhesions. This switch in adhesions confers a diminution of matrix degradation and reduced cell migration. Furthermore, reduced PAK4 expression causes a significant reduction in podosome number that cannot be rescued by kinase-dead PAK4, supporting a kinase-dependent role. Concomitant with PAK4 depletion, phosphorylation of Akt is perturbed, whereas a specific phospho-Akt signal is detected within the podosomes. Using superresolution analysis, we find that PAK4 specifically localizes in the podosome ring, nearer to the actin core than other ring proteins. We propose PAK4 kinase activity intersects with the Akt pathway at the podosome ring:core interface to drive regulation of macrophage podosome turnover.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Mieloides / Quinasas p21 Activadas / Podosomas Límite: Humans Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Mieloides / Quinasas p21 Activadas / Podosomas Límite: Humans Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos