RRC ID 68506
Author Murata-Hori M, Fukuta Y, Ueda K, Iwasaki T, Hosoya H.
Title HeLa ZIP kinase induces diphosphorylation of myosin II regulatory light chain and reorganization of actin filaments in nonmuscle cells.
Journal Oncogene
Abstract Dlk/ZIP kinase is a serine/threonine kinase highly homologous to DAP kinase. We have reported that HeLa ZIP kinase (hZIPK) phosphorylated the regulatory light chain of myosin II (MRLC) at both Ser19 and Thr18 in vitro. In this study, we demonstrate that hZIPK also induces the diphosphorylation of MRLC in nonmuscle cells. Peptide mapping revealed that transient transfection of hZIPK into HeLa cells caused diphosphorylation of MRLC. In contrast, transfection of the kinase inactive mutant of hZIPK did not induce any phosphorylation of MRLC. Using antibodies specific for mono- or diphosphorylated MRLC, we showed that diphosphorylated MRLC induced by the overexpression of hZIPK was concentrated in striking aggregates or bundles of actin filaments in HeLa cells, while monophosphorylated MRLC showed no prominent localization to these aggregates. Overexpression of hZIPK also induced dramatic changes in cell shape and disruption of nuclear morphology reminiscent of changes during apoptosis. These effects of hZIPK were suppressed by the coexpression of a mutant MRLC where both phosphorylation sites were replaced with alanine, indicating that the changes in actin organization were a consequence of MRLC diphosphorylation. These results suggested that hZIPK plays a role in regulating actin organization and cell morphology in non-muscles and at least part of its effects are mediated through the diphosphorylation of MRLC.
Volume 20(57)
Pages 8175-83
Published 2001-12-13
DOI 10.1038/sj.onc.1205055
PMID 11781833
MeSH Actin Cytoskeleton / ultrastructure* Actins / metabolism* Antibodies / immunology Antibody Specificity Apoptosis Regulatory Proteins Calcium-Calmodulin-Dependent Protein Kinases Cell Nucleus / ultrastructure Death-Associated Protein Kinases HeLa Cells Humans Microscopy, Fluorescence Muscles / metabolism Mutation Myosin Light Chains / immunology Myosin Light Chains / metabolism* Myosin Type II / metabolism* Peptide Mapping Phosphorylation Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / physiology* Transfection
IF 7.971
Human and Animal Cells HeLa(RCB0007) REF-RGB(RCB0165)