Inhibition of myosin light chain kinase by p21-activated kinase.
p21-activated kinases (PAKs) are implicated in the cytoskeletal changes induced by the Rho family of guanosine triphosphatases. Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin II that are regulated by myosin light chain kinase (MLCK)-mediated phosphorylation of the regulatory myosin light chain (MLC). p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity. MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1. These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation.
Sanders
L C
LC
Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Matsumura
F
F
Bokoch
G M
GM
de Lanerolle
P
P
D000818:Animals; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D048429:Cell Size; D006224:Cricetinae; D003599:Cytoskeleton / Q000502:physiology*; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009218:Myosins / Q000502:physiology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins; D054460:rho-Associated Kinases
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D010768:Phosphoserine; C004717:diacetylmonoxime; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D009218:Myosins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D003931:Diacetyl