A5088038458- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Erythrocyte Function and Pathophysiology
- Microtubule and mitosis dynamics
- Protein Kinase Regulation and GTPase Signaling
- Scheduling and Optimization Algorithms
- Phagocytosis and Immune Regulation
- Advanced Fluorescence Microscopy Techniques
- Skin and Cellular Biology Research
- Cardiomyopathy and Myosin Studies
- Manufacturing Process and Optimization
- Hippo pathway signaling and YAP/TAZ
- Pancreatic function and diabetes
- Neonatal Respiratory Health Research
- Liver Disease and Transplantation
- RNA Research and Splicing
- Reproductive System and Pregnancy
- Assembly Line Balancing Optimization
- Advanced Manufacturing and Logistics Optimization
- Metabolomics and Mass Spectrometry Studies
- Urban and spatial planning
- Energy, Environment, Agriculture Analysis
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Tohoku University
2015-2025
Niigata University Medical and Dental Hospital
2011-2022
Kogakuin University
1999-2017
Carnegie Mellon University
2016
Cincinnati Children's Hospital Medical Center
2012
Lung Institute
2012
Imperial College London
2012
Imperial College Healthcare NHS Trust
2012
St Mary's Hospital
2012
St. Mary's Hospital
2012
The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result its phosphorylation by LIM-kinase. was phosphorylated in N1E-115 neuroblastoma cells lysophosphatidic acid–induced, Rho-mediated neurite retraction. This sensitive to Y-27632, specific inhibitor...
LIM-kinase 1 (LIMK1) phosphorylates cofilin, an actin-depolymerizing factor, and regulates actin cytoskeletal reorganization. LIMK1 is activated by the small GTPase Rho its downstream protein kinase ROCK. We now report site of phosphorylation <i>In vitro</i> reaction revealed that active forms ROCK phosphorylated on threonine residue markedly increased cofilin-phosphorylating activity. A mutant (T508A) with replacement Thr-508 within activation loop domain alanine was neither nor Replacement...
Axl, Sky, and Mer, members of an Axl/Sky receptor tyrosine kinase subfamily, are typified by the cell adhesion molecule-related extracellular domain. The product growth arrest-specific gene 6 (Gas6), structurally homologous to anticoagulant protein S, was recently identified as ligand for Axl but Mer remained unknown. We have now obtained evidence that Gas6 can also function a Mer. Co-precipitation analysis, using soluble receptors (Axl-Fc, Sky-Fc, Mer-Fc) composed domain fused Fc...
Gas6, a product of growth arrest-specific gene 6, potentiates proliferation vascular smooth muscle cells and prevents cell death cells. It has been also demonstrated that Gas6 is ligand receptor tyrosine kinases Axl, Sky, Mer. contains γ-carboxyglutamic acid residues, which are found in some blood coagulation factors mediate the interaction with negatively charged phospholipid. In this study, we clarified specifically bound to phosphatidylserine binding was dependent on Ca2+ residues....
Growth cone motility and morphology are based on actin-filament dynamics. Cofilin plays an essential role for the rapid turnover of actin filaments by severing depolymerizing them. The activity cofilin is repressed phosphorylation at Ser3 LIM kinase (LIMK, in which acronym three gene products Lin-11, Isl-1, Mec-3) reactivated dephosphorylation phosphatases, termed Slingshot (SSH). We investigated roles cofilin, LIMK, SSH growth neurite extension expressing fluorescence protein-labeled LIMK1,...
Gas6, a ligand of receptor tyrosine kinases Axl, Sky, and Mer, potentiates cell proliferation prevents death. It also contains g-carboxylglutamic acid residues that mediate the interaction some blood coagulation factors with negatively charged phospholipids. In our previous study, we demonstrated Gas6 specifically binds to phosphatidylserine (PS) links Axl-expressing cells PS-coated surface. this further understand biological role PS, examined effect on uptake PS liposomes by macrophages....
Cofilin mediates lamellipodium extension and polarized cell migration by accelerating actin filament dynamics at the leading edge of migrating cells. is inactivated LIM kinase (LIMK)–1-mediated phosphorylation reactivated cofilin phosphatase Slingshot (SSH)-1L. In this study, we show that activity temporally spatially regulated LIMK1 SSH1L in chemokine-stimulated Jurkat T The knockdown suppressed chemokine-induced formation migration, whereas produced retained multiple lamellipodial...
To investigate the mechanisms of peroxisome assembly and molecular basis disorders, we isolated characterized a peroxisome-deficient CHO cell mutant, ZP139, which was found to belong human complementation group II, same as that our earlier ZP105. These mutants had phenotypic deficiency in import peroxisomal targeting signal type 1 (PTS1) proteins. Amino-terminal extension (PTS2)-mediated transport, including 3-ketoacyl coenzyme A thiolase, also defective ZP105 but not ZP139. PEX5 cDNA,...
Cofilin mediates lamellipodium extension and polarized cell migration by stimulating actin filament dynamics at the leading edge of migrating cells. is inactivated phosphorylation Ser-3 reactivated cofilin-phosphatase Slingshot-1L (SSH1L). Little known signaling mechanisms cofilin activation how this spatially regulated. Here, we show that activity SSH1L increases approximately 10-fold association with filaments, which indicates assembly per se triggers local thereby stimulates...
Cofilin stimulates actin filament disassembly and accelerates turnover. is also involved in stimulus-induced assembly during lamellipodium formation. However, it not clear whether this occurs by replenishing the monomer pool, through disassembly, or creating free barbed ends, its severing activity. Using photoactivatable Dronpa-actin, we show that cofilin producing more than half of all cytoplasmic monomers rate incorporation into tip dependent on size pool. Finally, cofilin-depleted cells,...
Cyclic stretch is an artificial model of mechanical force loading, which induces the reorientation vascular endothelial cells (ECs) and their stress fibers in a direction perpendicular to axis. Rho family GTPases are crucial for cyclic stretch-induced EC reorientation; however, mechanism underlying activation unknown. A screen short-hairpin RNAs targeting 63 Rho-guanine nucleotide exchange factors (Rho-GEFs) revealed that at least 11 Rho-GEFs (Abr, Alsin, ARHGEF10, Bcr, GEF-H1, LARG,...
Cofilin and its closely related protein, actin-depolymerizing factor (ADF), are key regulators of actin cytoskeleton dynamics that have been implicated in growth cone motility neurite extension. Cofilin/ADF inactivated by LIM kinase (LIMK)-catalyzed phosphorylation reactivated Slingshot (SSH)-catalyzed dephosphorylation. Here we examined the roles cofilin/ADF, LIMKs (LIMK1 LIMK2), SSHs (SSH1 SSH2) nerve (NGF)-induced Knockdown cofilin/ADF RNA interference almost completely inhibited...
To understand the intracellular role of G-actin concentration in stimulus-induced actin assembly and lamellipodium extension during cell migration, we developed a novel technique for quantifying spatiotemporal changes live cells, consisting sequential measurements fluorescent decay after photoactivation (FDAP) Dronpa-labeled actin. Cytoplasmic concentrations decreased by ∼40% immediately stimulation thereafter area extended. The extent loss correlated linearly with unstimulated even at much...
Abstract Background: Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser‐3 LIM‐kinases and reactivated dephosphorylation family protein phosphatases, termed Slingshot (SSH). Results: We have identified two novel isoforms SSHs, SSH‐2L SSH‐3L characterized them in comparison with SSH‐1L that was previously reported. SSH‐2L, but not SSH‐3L, tightly bound to co‐localized filaments. When expressed cultured cells, SSH‐1L, decreased the level...