Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase.
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.
Owen
Katherine A
KA
Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA.
Pixley
Fiona J
FJ
Thomas
Keena S
KS
Vicente-Manzanares
Miguel
M
Ray
Brianne J
BJ
Horwitz
Alan F
AF
Parsons
J Thomas
JT
Beggs
Hilary E
HE
Stanley
E Richard
ER
Bouton
Amy H
AH
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism / Q000502:physiology*; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
D009479:Neuropeptides; C484602:Rac1 protein, mouse; D017978:Receptors, Growth Factor; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; C496051:Ptk2 protein, mouse; C496053:Ptk2b protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein