Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase

Katherine A. Owen, Fiona J. Pixley, Keena S. Thomas, Miguel Vicente-Manzanares, Brianne J. Ray, Alan F. Horwitz, J. Thomas Parsons, Hilary E. Beggs, E. Richard Stanley, Amy H. Bouton

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Macrophages are a key component of the innate immune system. In this study, we investigate how focal adhesion kinase (FAK) and the related kinase Pyk2 integrate adhesion signaling and growth factor receptor signaling to regulate diverse macrophage functions. Primary bone marrow macrophages isolated from mice in which FAK is conditionally deleted from cells of the myeloid lineage exhibited elevated protrusive activity, altered adhesion dynamics, impaired chemotaxis, elevated basal Rac1 activity, and a marked inability to form stable lamellipodia necessary for directional locomotion. The contribution of FAK to macrophage function in vitro was substantiated in vivo by the finding that recruitment of monocytes to sites of inflammation was impaired in the absence of FAK. Decreased Pyk2 expression in primary macrophages also resulted in a diminution of invasive capacity. However, the combined loss of FAK and Pyk2 had no greater effect than the loss of either molecule alone, indicating that both kinases function within the same pathway to promote invasion.

Original languageEnglish (US)
Pages (from-to)1275-1287
Number of pages13
JournalJournal of Cell Biology
Volume179
Issue number6
DOIs
StatePublished - Dec 17 2007

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Focal Adhesion Protein-Tyrosine Kinases
Macrophages
Phosphotransferases
Pseudopodia
Growth Factor Receptors
Cell Lineage
Chemotaxis
Locomotion
Monocytes
Immune System
Bone Marrow
Inflammation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Owen, K. A., Pixley, F. J., Thomas, K. S., Vicente-Manzanares, M., Ray, B. J., Horwitz, A. F., ... Bouton, A. H. (2007). Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. Journal of Cell Biology, 179(6), 1275-1287. https://doi.org/10.1083/jcb.200708093

Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. / Owen, Katherine A.; Pixley, Fiona J.; Thomas, Keena S.; Vicente-Manzanares, Miguel; Ray, Brianne J.; Horwitz, Alan F.; Parsons, J. Thomas; Beggs, Hilary E.; Stanley, E. Richard; Bouton, Amy H.

In: Journal of Cell Biology, Vol. 179, No. 6, 17.12.2007, p. 1275-1287.

Research output: Contribution to journalArticle

Owen, KA, Pixley, FJ, Thomas, KS, Vicente-Manzanares, M, Ray, BJ, Horwitz, AF, Parsons, JT, Beggs, HE, Stanley, ER & Bouton, AH 2007, 'Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase', Journal of Cell Biology, vol. 179, no. 6, pp. 1275-1287. https://doi.org/10.1083/jcb.200708093
Owen, Katherine A. ; Pixley, Fiona J. ; Thomas, Keena S. ; Vicente-Manzanares, Miguel ; Ray, Brianne J. ; Horwitz, Alan F. ; Parsons, J. Thomas ; Beggs, Hilary E. ; Stanley, E. Richard ; Bouton, Amy H. / Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. In: Journal of Cell Biology. 2007 ; Vol. 179, No. 6. pp. 1275-1287.
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