PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and cell chemotaxis.
Serine/threonine p21-activated kinase is an effector of Rac with a key role in the regulation of cytoskeletal organization. Non-muscle myosin II is a molecular motor, which is an important component of the cytoskeleton. Non-muscle myosin II-B plays a major role in cell motility and chemotaxis. We investigated the role of Rac and p21-activated kinase 1 (PAK1) in the regulation of myosin II-B in prostate cancer cells in response to epidermal growth factor (EGF) stimulation. We found that both Rac and PAK1 affect EGF-dependent non-muscle heavy chain II-B localization and cell morphology. We further found that a dominant negative mutant of PAK1 significantly inhibits EGF-dependent myosin II-B heavy chains phosphorylation and filament disassembly. Furthermore, cells expressing the dominant negative mutant exhibited an increase in EGF-dependent myosin light chain phosphorylation and diminished chemotaxis towards EGF. To our knowledge this is the first report exploring the role of PAK1 in the regulation of both non-muscle myosin II-B heavy chains and light chains. Furthermore, the data presented here suggest that PAK1 plays a crucial role in the regulation of cell morphology and chemotaxis by regulating the phosphorylation and cellular localization of myosin II-B.
Even-Faitelson
Liron
L
Department of Biochemistry, Institute of Medical Sciences, Faculty of Medicine, The Hebrew University, P.O.B. 12272, Jerusalem 91120, Israel.
Rosenberg
Michael
M
Ravid
Shoshana
S
D008841:Actin Cytoskeleton / Q000378:metabolism*; D045744:Cell Line, Tumor; D048430:Cell Shape; D002633:Chemotaxis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D018995:Myosin Heavy Chains / Q000032:analysis / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000502:physiology
D018994:Myosin Light Chains; D004815:Epidermal Growth Factor; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D024501:Nonmuscle Myosin Type IIB; D018995:Myosin Heavy Chains; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein