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 dynamic changes in the cytoskeleton. These migration-dependent cytoskeletal changes are partly mediated by p21-activated protein kinases (PAKs). At least four closely related isoforms, PAK1, PAK2, PAK3, and PAK4, exist in mammalian cells. In smooth muscle cells, little is known about the expression, activation, or ability of PAKs to regulate migration. Our study revealed the existence of three PAK isoforms in cultured tracheal smooth muscle cells (TSMCs). Additionally, we constructed adenoviral vectors encoding wild type and a catalytically inactive PAK1 mutant to investigate PAK activation and its role in TSMC migration. Stimulation of TSMCs with platelet-derived growth factor (PDGF) increased the activity of PAK1 over time. Overexpression of mutant PAK1 blocked PDGF-induced chemotactic cell migration. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) in cells overexpressing wild-type PAK1 was similar to vector controls; however, p38 MAPK phosphorylation was severely reduced by overexpression of the PAK1 mutant. Collectively, these results suggest a role for PAK1 in chemotactic TSMC migration that involves catalytic activity and may require signaling to p38 MAPK among other pathways.
Dechert
M A
MA
Cell and Molecular Biology Program, School of Medicine, University of Nevada, Reno, Nevada 89557-0046, USA.
Holder
J M
JM
Gerthoffer
W T
WT
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004285:Dogs; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000166:cytology; D014161:Transduction, Genetic; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases
D016895:Culture Media, Serum-Free; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases