Inhibition of myosin light chain kinase by p21-activated kinase

p21-activated kinases (PAKs) are implicated in the cytoskeletal changes ind uced by the Rho family of guanosine triphosphatases. Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin II that are reg ulated by myosin light chain kinase (MLCK)-mediated phosphorylation of the regulatory myosin Light chain (MLC). p21-activated kinase 1 (PAK1) phosphor ylates MLCK, resulting in decreased MLCK activity. MLCK activity and MLC ph osphorylation were decreased, and cell spreading was inhibited in baby hams ter kidney-21 and HeLa cells expressing constitutively active PAK1. These d ata indicate that MLCK is a target for PAKs and that PAKs may regulate cyto skeletal dynamics by decreasing MLCK activity and MLC phosphorylation.