title: Myosin ii light chain phosphorylation regulates membrane localization and apoptotic signaling of tumor necrosis factor receptor-1.
abstract: Activation of myosin II by myosin light chain kinase (MLCK) produces the force for many cellular processes including muscle contraction, mitosis, migration, and other cellular shape changes. The results of this study show that inhibition or potentiation of myosin II activation via over-expression of a dominant negative or wild type MLCK can delay or accelerate tumor necrosis factor-alpha (TNF)-induced apoptotic cell death in cells. Changes in the activation of caspase-8 that parallel changes in regulatory light chain phosphorylation levels reveal that myosin II motor activities regulate TNF receptor-1 (TNFR-1) signaling at an early step in the TNF death signaling pathway. Treatment of cells with either ionomycin or endotoxin (lipopolysaccharide) leads to activation of myosin II and increased translocation of TNFR-1 to the plasma membrane independent of TNF signaling. The results of these studies establish a new role for myosin II motor activity in regulating TNFR-1-mediated apoptosis through the translocation of TNFR-1 to or within the plasma membrane.
authors.affiliation: Department of Cellular and Integrative Physiology and the Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: S J
authors.initials: SJ
authors.lastname: Atkinson
authors.forename: J A
authors.initials: JA
authors.lastname: Marrs
authors.forename: P J
authors.initials: PJ
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D029681:Arabidopsis Proteins; D001710:Biotin / Q000378:metabolism; D015153:Blotting, Western; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004285:Dogs; D004731:Endotoxins / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D018994:Myosin Light Chains / Q000737:chemistry* / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D011485:Protein Binding; D021381:Protein Transport; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D015703:Antigens, CD; D029681:Arabidopsis Proteins; D004731:Endotoxins; D007476:Ionophores; D008070:Lipopolysaccharides; D018994:Myosin Light Chains; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D015759:Ionomycin; D001710:Biotin; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D009218:Myosins