Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase

Cell movement requires forces generated by non-muscle myosin II (NM II) for coordinated protrusion and retraction. The Cdc42/Rac effector MRCK regulates a specific actomyosin network in the lamella essential for cell protrusion and migration. Together with the Rho effector ROK required for cell rear...

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Bibliographic Details
Published in:	FEBS letters Vol. 585; no. 9; pp. 1260 - 1268
Main Authors:	Tan, Ivan, Lai, Jesyin, Yong, Jeffery, Li, Sam F.Y., Leung, Thomas
Format:	Journal Article
Language:	English
Published:	England Elsevier B.V 06-05-2011
Subjects:	Actomyosin Actomyosin - metabolism Amides - pharmacology Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Benzophenanthridines - chemistry Benzophenanthridines - pharmacology Biocatalysis - drug effects Cell Line, Tumor Cell migration Cell Movement - drug effects Cercopithecus aethiops COS Cells Cytoskeleton - drug effects Cytoskeleton - metabolism Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology HeLa Cells Humans Immunoblotting Microscopy, Fluorescence Molecular Structure Myosins - metabolism Myotonin-Protein Kinase Phosphorylation - drug effects Protein kinase Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Pyridines - pharmacology Recombinant Proteins - antagonists & inhibitors Recombinant Proteins - metabolism rho-Associated Kinases - antagonists & inhibitors rho-Associated Kinases - metabolism Serine - metabolism Actomyosin Protein kinase Cell migration
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Summary:	Cell movement requires forces generated by non-muscle myosin II (NM II) for coordinated protrusion and retraction. The Cdc42/Rac effector MRCK regulates a specific actomyosin network in the lamella essential for cell protrusion and migration. Together with the Rho effector ROK required for cell rear retraction, they cooperatively regulate cell motility and tumour cell invasion. Despite the increasing importance of ROK inhibitors for both experimental and clinical purposes, there is a lack of specific inhibitors for other related kinases such as MRCK. Here, we report the identification of chelerythrine chloride as a specific MRCK inhibitor. Its ability to block cellular activity of MRCK resulted in the specific loss of NM II-associated MLC phosphorylation in the lamella, and the consequential suppression of cell migration. DMPK phosphorylates MYPT by protein kinase assay (View interaction) PAK alpha phosphorylates MLC by protein kinase assay (View interaction) MRCK alpha phosphorylates MLC by protein kinase assay (View interaction) CRIK phosphorylates MLC by protein kinase assay (View interaction) MRCK beta phosphorylates MLC by protein kinase assay (View interaction) ROK alpha phosphorylates MLC by protein kinase assay (View Interaction 1, 2) MRCK beta phosphorylates MYPT by protein kinase assay (View interaction) MRCK alpha phosphorylates MYPT by protein kinase assay (View interaction) ROK alpha phosphorylates MYPT by protein kinase assay (View interaction) MLCK phosphorylates MLC by protein kinase assay (View interaction)
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-5793 1873-3468
DOI:	10.1016/j.febslet.2011.03.054