p21-activated kinase 1 participates in tracheal smooth muscle cell migration by signaling to p38 MAPK

Cell migration contributes to many physiological processes and requires dyn amic changes in the cytoskeleton. These migration-dependent cytoskeletal ch anges are partly mediated by p21-activated protein kinases (PAKs). At least four closely related isoforms, PAK1, PAK2, PAK3, and PAK4, exist in mammal ian cells. In smooth muscle cells, little is known about the expression, ac tivation, or ability of PAKs to regulate migration. Our study revealed the existence of three PAK isoforms in cultured tracheal smooth muscle cells (T SMCs). Additionally, we constructed adenoviral vectors encoding wild type a nd a catalytically inactive PAK1 mutant to investigate PAK activation and i ts role in TSMC migration. Stimulation of TSMCs with platelet-derived growt h factor (PDGF) increased the activity of PAK1 over time. Overexpression of mutant PAK1 blocked PDGF-induced chemotactic cell migration. Phosphorylati on of p38 mitogen-activated protein kinase (MAPK) in cells overexpressing w ild-type PAK1 was similar to vector controls; however, p38 MAPK phosphoryla tion was severely reduced by overexpression of the PAK1 mutant. Collectivel y, these results suggest a role for PAK1 in chemotactic TSMC migration that involves catalytic activity and may require signaling to p38 MAPK among ot her pathways.