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

Abstract

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. Structured summary of protein interactions 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)