myosin light chains

Summary

Summary: The smaller subunits of MYOSINS that bind near the head groups of MYOSIN HEAVY CHAINS. The myosin light chains have a molecular weight of about 20 KDa and there are usually one essential and one regulatory pair of light chains associated with each heavy chain. Many myosin light chains that bind calcium are considered "calmodulin-like" proteins.

Top Publications

  1. pmc Ablation of ventricular myosin regulatory light chain phosphorylation in mice causes cardiac dysfunction in situ and affects neighboring myofilament protein phosphorylation
    Sarah B Scruggs
    Department of Physiology and Biophysics and Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Biol Chem 284:5097-106. 2009
  2. ncbi Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase
    Andrew P Somlyo
    Dept of Molecular Physiology and Biological Physics, Univ of Virginia, PO Box 800736, Charlottesville, VA 22908 0736
    Physiol Rev 83:1325-58. 2003
  3. ncbi Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase)
    M Amano
    Division of Signal Transduction, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma 630 01
    J Biol Chem 271:20246-9. 1996
  4. pmc Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts
    G Totsukawa
    Department of Molecular Biology and Biochemistry, Rutgers University, Nelson Lab, Busch Campus, Piscataway, New Jersey 08855, USA
    J Cell Biol 150:797-806. 2000
  5. pmc Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II
    Shigeko Yamashiro
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08855, USA
    Mol Biol Cell 14:1745-56. 2003
  6. ncbi Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
    K Kimura
    Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630 01, Japan
    Science 273:245-8. 1996
  7. pmc ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles
    Yoshihiko Shimizu
    Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo ku, Kyoto 606 8501, Japan
    J Cell Biol 168:941-53. 2005
  8. pmc The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy
    Adam M Jacques
    Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Guy Scadding Building, Dovehouse Street, London, UK
    Cardiovasc Res 79:481-91. 2008
  9. ncbi Rho and ROCK signaling in VEGF-induced microvascular endothelial hyperpermeability
    Hengrui Sun
    Department of Surgery, University of California at Davis School of Medicine, Sacramento, California, USA
    Microcirculation 13:237-47. 2006
  10. ncbi Inhibition of myosin light chain kinase by p21-activated kinase
    L C Sanders
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 283:2083-5. 1999

Research Grants

  1. Myosin ELC, a novel therapeutic target for FHC
    Danuta Szczesna-Cordary; Fiscal Year: 2013
  2. Structual and Calcium Regulatory Proteins in Sarcopenia
    LaDora V Thompson; Fiscal Year: 2012
  3. LENGTH REGULATION OF CARDIAC CONTRACTION
    Donald Martyn; Fiscal Year: 2010
  4. The role of RhoA and its targets in craniofacial cartilage morphogenesis
    BARBARA SISSON; Fiscal Year: 2010
  5. CGMP DEPENDENT PROTEIN KINASE IN VASCULAR BIOLOGY
    HOWARD SURKS; Fiscal Year: 2003
  6. ETIOLOGY AND DEVELOPMENT OF CONGENITAL HEART DISEASES
    Donald Patterson; Fiscal Year: 1999
  7. EFFECT OF TSH ON THYROID METABOLISM
    WILLIAM DEERY; Fiscal Year: 1991
  8. MOLECULAR MECHANISM OF THE REGULATION IN SMOOTH MUSCLE
    Mitsuo Ikebe; Fiscal Year: 1991
  9. MODULATORS OF MUSCLE CROSS-BRIDGE FUNCTION
    Roger Cooke; Fiscal Year: 2009
  10. CONTRACTILE PROTEIN EXPRESSION IN FAILING HUMAN HEART
    Michael Bristow; Fiscal Year: 2002

Detail Information

Publications293 found, 100 shown here

  1. pmc Ablation of ventricular myosin regulatory light chain phosphorylation in mice causes cardiac dysfunction in situ and affects neighboring myofilament protein phosphorylation
    Sarah B Scruggs
    Department of Physiology and Biophysics and Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Biol Chem 284:5097-106. 2009
    ..Our data also indicate that the lack of RLC phosphorylation promotes compensatory changes in MyBP-C and TnI phosphorylation, which when normalized do not restore function...
  2. ncbi Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase
    Andrew P Somlyo
    Dept of Molecular Physiology and Biological Physics, Univ of Virginia, PO Box 800736, Charlottesville, VA 22908 0736
    Physiol Rev 83:1325-58. 2003
    ..It is a potentially important therapeutic target and a subject for translational research...
  3. ncbi Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase)
    M Amano
    Division of Signal Transduction, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma 630 01
    J Biol Chem 271:20246-9. 1996
    ..The activated Rho-kinase subsequently phosphorylates MLC. This may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction...
  4. pmc Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts
    G Totsukawa
    Department of Molecular Biology and Biochemistry, Rutgers University, Nelson Lab, Busch Campus, Piscataway, New Jersey 08855, USA
    J Cell Biol 150:797-806. 2000
    ..At the cell periphery, on the other hand, MLCK but not ROCK appears to be the kinase responsible for phosphorylating MLC. These results suggest that ROCK and MLCK play distinct roles in spatial regulation of MLC phosphorylation...
  5. pmc Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II
    Shigeko Yamashiro
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08855, USA
    Mol Biol Cell 14:1745-56. 2003
    ..Because citron kinase is localized in cleavage furrows, citron kinase may be involved in regulating di-phosphorylation of MLC during cytokinesis...
  6. ncbi Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
    K Kimura
    Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630 01, Japan
    Science 273:245-8. 1996
    ..Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase...
  7. pmc ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles
    Yoshihiko Shimizu
    Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo ku, Kyoto 606 8501, Japan
    J Cell Biol 168:941-53. 2005
    ..These results suggest that ROCK-I regulates closure of the eyelids and ventral body wall through organization of actomyosin bundles...
  8. pmc The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy
    Adam M Jacques
    Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Guy Scadding Building, Dovehouse Street, London, UK
    Cardiovasc Res 79:481-91. 2008
    ....
  9. ncbi Rho and ROCK signaling in VEGF-induced microvascular endothelial hyperpermeability
    Hengrui Sun
    Department of Surgery, University of California at Davis School of Medicine, Sacramento, California, USA
    Microcirculation 13:237-47. 2006
    ..They also investigated myosin light chain (MLC) phosphorylation and actin polymerization, two well-characterized targets of the Rho-ROCK pathway that are implicated in the regulation of endothelial barrier function...
  10. ncbi Inhibition of myosin light chain kinase by p21-activated kinase
    L C Sanders
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 283:2083-5. 1999
    ..These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation...
  11. pmc Cardiac myosin light chain kinase is necessary for myosin regulatory light chain phosphorylation and cardiac performance in vivo
    Peiguo Ding
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 285:40819-29. 2010
    ..Thus, cMLCK appears to be the predominant protein kinase that maintains basal RLC phosphorylation that is required for normal physiological cardiac performance in vivo...
  12. pmc Myosin light chain kinase and the role of myosin light chain phosphorylation in skeletal muscle
    James T Stull
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, 75390 9040, USA
    Arch Biochem Biophys 510:120-8. 2011
    ..Moreover, RLC phosphorylation-mediated enhancements may interact with neural strategies for human skeletal muscle activation to ameliorate either central or peripheral aspects of fatigue...
  13. pmc The GTP binding proteins Gem and Rad are negative regulators of the Rho-Rho kinase pathway
    Yvona Ward
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    J Cell Biol 157:291-302. 2002
    ..In addition, Gem reverted the anchorage-independent growth and invasiveness of Dbl-transformed fibroblasts. These results identify physiological roles for Gem and Rad in cytoskeletal regulation mediated by ROK...
  14. ncbi Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle
    K Poetter
    Inherited Cardiac Diseases Section, NHLBI, NIH Bethesda, Maryland 20892 1650, USA
    Nat Genet 13:63-9. 1996
    ....
  15. pmc Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease
    Farah Sheikh
    Department of Medicine, UCSD, La Jolla, California 92093 0613C, USA
    J Clin Invest 122:1209-21. 2012
    ..Thus, there is a direct and early role for Mlc2 phosphorylation in regulating actin-myosin interactions in striated muscle contraction, and dephosphorylation of Mlc2 or loss of these mechanisms can play a critical role in heart failure...
  16. pmc Two distinct myosin light chain structures are induced by specific variations within the bound IQ motifs-functional implications
    Mohammed Terrak
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    EMBO J 22:362-71. 2003
    ..The resulting 'free' N-lobes of myosin light chains in the extended conformation could mediate the formation of ternary complexes during protein localization ..
  17. pmc ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells
    Yuepeng Wang
    Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
    Circ Res 104:531-40. 2009
    ..These data support that although the ROCK isoforms both regulate MLCP and myosin light chain phosphorylation through different mechanisms, they have distinct roles in VSMC function...
  18. pmc IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction
    Fengjun Wang
    State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, China
    Gastroenterology 131:1153-63. 2006
    ..The aim of this study was to determine the signaling pathways by which TNF causes intestinal epithelial barrier loss...
  19. ncbi Movement of membrane domains and requirement of membrane signaling molecules for cytokinesis
    Michelle M Ng
    Department of Biology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, Massachusetts 02467, USA
    Dev Cell 9:781-90. 2005
    ..These studies suggest that membrane domains at the cleavage furrow possess a signaling pathway that contributes to cytokinesis...
  20. pmc Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration
    Daniel R Croft
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 168:245-55. 2005
    ....
  21. ncbi Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis
    Chengqun Huang
    Institute of Molecular Medicine and Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0641, USA
    Development 130:6111-9. 2003
    ..Our results unequivocally demonstrate that normal cardiac function is directly linked to normal morphogenic development of heart and vasculature. These data have important implications for the etiology of congenital heart disease...
  22. pmc Identification of cardiac-specific myosin light chain kinase
    Jason Y Chan
    Department of Physiology and Functional Genomics, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610 0274, USA
    Circ Res 102:571-80. 2008
    ..Both overexpression and knockdown of cardiac MLCK in cultured cardiomyocytes revealed that cardiac MLCK is likely a new regulator of MLC2 phosphorylation, sarcomere organization, and cardiomyocyte contraction...
  23. pmc Toxoplasma gondii myosin A and its light chain: a fast, single-headed, plus-end-directed motor
    Angelika Herm-Götz
    Zentrum fur Molekulare Biologie, Universitat Heidelberg, Im Neuenheimer Feld 282, Germany
    EMBO J 21:2149-58. 2002
    ..3 nm with a velocity of 5.2 microm/s towards the plus end of actin filaments. TgMyoA is the first fast, single-headed myosin and fulfils all the requirements for power parasite gliding...
  24. pmc The anaphase-promoting complex promotes actomyosin-ring disassembly during cytokinesis in yeast
    Gregory H Tully
    Department of Physiology, University of California, San Francisco, CA 94158, USA
    Mol Biol Cell 20:1201-12. 2009
    ..Deletion of CDH1 also exacerbates actomyosin-ring disassembly defects in cells with mutations in the myosin light-chain Mlc2, suggesting that Mlc2 and the APC employ independent mechanisms to promote ring disassembly during cytokinesis...
  25. pmc Diastolic dysfunction in familial hypertrophic cardiomyopathy transgenic model mice
    Theodore P Abraham
    Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA
    Cardiovasc Res 82:84-92. 2009
    ....
  26. ncbi Regulatory light chain phosphorylation and the assembly of myosin II into the cytoskeleton of microcapillary endothelial cells
    J Kolega
    Department of Anatomy and Cell Biology, State University of New York at Buffalo, School of Medicine and Biomedical Sciences 14214, USA
    Cell Motil Cytoskeleton 43:255-68. 1999
    ..These observations suggest that assembly of myosin II into cytoskeletal structures, where it can generate and resist forces, is regulated in vivo by phosphorylation of myosin light chains at serine 19/threonine 18.
  27. ncbi Microtubule disassembly induces cytoskeletal remodeling and lung vascular barrier dysfunction: role of Rho-dependent mechanisms
    Anna A Birukova
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Cell Physiol 201:55-70. 2004
    ....
  28. pmc Heavy and light roles: myosin in the morphogenesis of the heart
    Jennifer England
    School of Biomedical Sciences, University of Nottingham, Queens Medical Centre, Derby Road, Nottingham, NG7 2UH, UK
    Cell Mol Life Sci 70:1221-39. 2013
    ..The human molecular genetics of the myosins will also be reviewed...
  29. ncbi Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain
    R Tohtong
    Department of Biochemistry, Faculty of Science, Mahidol University, Phya Thai, Bangkok, Thailand
    Prostate Cancer Prostatic Dis 6:212-6. 2003
    ....
  30. ncbi Selective requirement of myosin light chain 2v in embryonic heart function
    J Chen
    Department of Medicine, University of California at San Diego, School of Medicine, La Jolla, California 92093 0613, USA
    J Biol Chem 273:1252-6. 1998
    ....
  31. pmc Fibronectin matrix assembly requires distinct contributions from Rho kinases I and -II
    Atsuko Yoneda
    Division of Biomedical Sciences, Imperial College London, London SW7 2AZ, United Kingdom
    Mol Biol Cell 18:66-75. 2007
    ..Together, two rho kinases contribute to fibronectin matrix assembly in a different manner and cortical myosin II-driven contractility, but not stress fibers, may be critical in this activity...
  32. pmc Direct observation of the myosin Va recovery stroke that contributes to unidirectional stepping along actin
    Katsuyuki Shiroguchi
    Department of Physics, Faculty of Science and Engineering, Waseda University, Tokyo, Japan
    PLoS Biol 9:e1001031. 2011
    ..Thus, the recovery stroke contributes to unidirectional stepping of myosin Va...
  33. pmc Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors
    Rongshi Li
    Department of Drug Discovery, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA
    J Med Chem 55:2474-8. 2012
    ..Compounds 18 and 24 inhibited potently the phosphorylation of the ROCK substrate MLC2 in intact human breast cancer cells...
  34. pmc Myosin light chain kinase mediates intestinal barrier disruption following burn injury
    Chuanli Chen
    State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Burn Research, Third Military Medical University, Southwest Hospital, Chongqing, China
    PLoS ONE 7:e34946. 2012
    ..We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction...
  35. doi Protective role of oligomycin against intestinal epithelial barrier dysfunction caused by IFN-γ and TNF-α
    Hang Liu
    State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, China
    Cell Physiol Biochem 29:799-808. 2012
    ..The mechanism by which oligomycin protects intestinal barrier function may, at least in part, be attributed to block the up-regulated MLCK transcription and protein expression induced by IFN-γ and TNF-α...
  36. pmc Attenuated fatigue in slow twitch skeletal muscle during isotonic exercise in rats with chronic heart failure
    Morten Munkvik
    Institute for Experimental Medical Research, Oslo University Hospital, Ulleval, Oslo, Norway
    PLoS ONE 6:e22695. 2011
    ..This observation is in striking contrast to previous reports which have employed isometric contractions to induce fatigue...
  37. pmc Chemical genetics of zipper-interacting protein kinase reveal myosin light chain as a bona fide substrate in permeabilized arterial smooth muscle
    Lori D Moffat
    Smooth Muscle Research Group and the Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4Z6, Canada
    J Biol Chem 286:36978-91. 2011
    ..LC(20) was thereby confirmed as a direct target of ZIPK; however, no phosphorylation of MYPT1 was detected. We conclude that ZIPK is involved in the regulation of smooth muscle contraction through direct phosphorylation of LC(20)...
  38. pmc Simultaneous stretching and contraction of stress fibers in vivo
    Lynda J Peterson
    Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Mol Biol Cell 15:3497-508. 2004
    ..In the periphery, the banding patterns for both proteins were shorter, whereas in central regions, where stretching occurred, the bands were wider...
  39. ncbi Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing
    M Sebbagh
    INSERM U461, Faculte de Pharmacie, 92296 Chatenay Malabry, France
    Nat Cell Biol 3:346-52. 2001
    ..We also show that expression of active truncated ROCK I induces cell blebbing. Thus, activation of ROCK I by caspase-3 seems to be responsible for bleb formation in apoptotic cells...
  40. doi MR-1 modulates proliferation and migration of human hepatoma HepG2 cells through myosin light chains-2 (MLC2)/focal adhesion kinase (FAK)/Akt signaling pathway
    Kaihuan Ren
    Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
    J Biol Chem 283:35598-605. 2008
    ..This study suggested that overexpression of MR-1 was associated with cancer cell proliferation and migration through MLC2 and that MR-1 might be a potential cancer therapeutic target...
  41. ncbi GEF-H1 is involved in agonist-induced human pulmonary endothelial barrier dysfunction
    Anna A Birukova
    Sect of Pulmonary and Critical Care, Dept of Medicine, Biological Sciences Div, Univ of Chicago, 929 E 57th St, W410, Chicago, IL 60637, USA
    Am J Physiol Lung Cell Mol Physiol 290:L540-8. 2006
    ....
  42. pmc Differential phosphorylation of myosin light chain (Thr)18 and (Ser)19 and functional implications in platelets
    T M Getz
    Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA
    J Thromb Haemost 8:2283-93. 2010
    ..Myosin IIA is an essential platelet contractile protein that is regulated by phosphorylation of its regulatory light chain (MLC) on residues (Thr)18 and (Ser)19 via the myosin light chain kinase (MLCK)...
  43. ncbi Disruption of Rho signal transduction upon cell detachment
    Xiang Dong Ren
    Department of Dermatology, SUNY at Stony Brook, Stony Brook, NY 11794, USA
    J Cell Sci 117:3511-8. 2004
    ..The convergence of signals from soluble factors and cell adhesion might therefore occur at the point of MLC phosphorylation, providing an effective mechanism for dynamic control of contractility during cell migration...
  44. pmc Deficiency in myosin light-chain phosphorylation causes cytokinesis failure and multipolarity in cancer cells
    Q Wu
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Oncogene 29:4183-93. 2010
    ..These results for the first time define the molecular defects leading to divisional failure in cancer cells...
  45. doi Inhibition of RhoA but not ROCK induces chondrogenesis of chick limb mesenchymal cells
    Min Jung Kim
    Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702 701, South Korea
    Biochem Biophys Res Commun 418:500-5. 2012
    ..To further investigate the role of RhoA and ROCK in the chondrogenesis, we examined the RhoA-ROCK-myosin light chains (MLC) pathway in low density culture of chick limb bud mesenchymal cells...
  46. pmc Altered kinetics of contraction in skeletal muscle fibers containing a mutant myosin regulatory light chain with reduced divalent cation binding
    G M Diffee
    Department of Physiology, University of Wisconsin, Madison 53706, USA
    Biophys J 71:341-50. 1996
    ..These results suggest that divalent cation binding to myosin RLC plays an important role in modulating the kinetics of cross-bridge attachment and detachment...
  47. pmc Myosin regulatory light chain phosphorylation attenuates cardiac hypertrophy
    Jian Huang
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 283:19748-56. 2008
    ..Thus, increased myosin RLC phosphorylation per se does not cause cardiac hypertrophy and probably inhibits physiological and pathophysiological hypertrophy by contributing to enhanced contractile performance and efficiency...
  48. pmc Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice
    Wei Qi He
    Model Animal Research Center and MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China
    Gastroenterology 135:610-20. 2008
    ..We generated tamoxifen-inducible and smooth muscle-specific MLCK knockout (KO) mice and provide direct loss-of-function evidence that shows the primary importance of MLCK in phasic smooth muscle contractions...
  49. doi MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9
    Laure Gilles
    INSERM, U790, Villejuif, France
    Blood 114:4221-32. 2009
    ..Finally, the use of a shRNA to decrease MYL9 expression showed that MYL9 was involved in proplatelet formation. MAL/SRF complex is thus involved in platelet formation and megakaryocyte migration by regulating MYL9 and MMP9...
  50. pmc Apolipoprotein(a), through its strong lysine-binding site in KIV(10'), mediates increased endothelial cell contraction and permeability via a Rho/Rho kinase/MYPT1-dependent pathway
    Taewoo Cho
    Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
    J Biol Chem 283:30503-12. 2008
    ..Studies are ongoing to further dissect the molecular basis of these findings...
  51. ncbi The E22K mutation of myosin RLC that causes familial hypertrophic cardiomyopathy increases calcium sensitivity of force and ATPase in transgenic mice
    Danuta Szczesna-Cordary
    Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33136, USA
    J Cell Sci 118:3675-83. 2005
    ....
  52. pmc Role of p38 MAPK in burn-induced intestinal barrier breakdown
    Todd W Costantini
    Division of Trauma, Surgical Critical Care, and Burns, Department of Surgery, University of California San Diego School of Medicine, San Diego, CA 92103 8896, USA
    J Surg Res 156:64-9. 2009
    ....
  53. doi Blockade of hypoxia-inducible factor-1α by YC-1 attenuates interferon-γ and tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction
    Hang Liu
    State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
    Cytokine 56:581-8. 2011
    ..YC-1 may be a potential agent for treatment of intestinal barrier disruption in inflammation...
  54. ncbi Oxytocin-induced phosphorylation of myosin light chain is mediated by extracellular calcium influx in pregnant rat myometrium
    H Shojo
    Department of Forensic Science, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
    J Mol Recognit 14:401-5. 2001
    ..Our results clearly indicate that extracellular Ca(2+) influx, rather than release from Ca(2+) storage sites, is essential for oxytocin-induced MLC phosphorylation...
  55. ncbi Inhibition by Rho-kinase and protein kinase C of myosin phosphatase is involved in thrombin-induced shape change of megakaryocytic leukemia cell line UT-7/TPO
    Akira Yazaki
    The 2nd Department of Internal Medicine, Mie University School of Medicine, Mie 514 8507, Japan
    Cell Signal 17:321-30. 2005
    ....
  56. pmc Quantification of rapid Myosin regulatory light chain phosphorylation using high-throughput in-cell Western assays: comparison to Western immunoblots
    Hector N Aguilar
    Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    PLoS ONE 5:e9965. 2010
    ....
  57. doi cAMP/PKA antagonizes thrombin-induced inactivation of endothelial myosin light chain phosphatase: role of CPI-17
    Muhammad Aslam
    Physiologisches Institut, Justus Liebig Universitat, Aulweg 129, Giessen, Germany
    Cardiovasc Res 87:375-84. 2010
    ..To date, the mechanisms of cAMP-mediated MLCP activation are only partially understood. Here the contribution of two cAMP effectors, PKA and Epac, in the regulation of endothelial contractile machinery and barrier function was studied...
  58. ncbi Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins
    J van der Velden
    Laboratory for Physiology, Institute for Cardiovascular Research ICaR VU, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
    Cardiovasc Res 57:37-47. 2003
    ..In the present study an attempt was made to reveal to what extent protein alterations contribute to the increased Ca(2+)-responsiveness in human heart failure...
  59. pmc Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton
    Dalit Barkan
    Laboratory of Cell Biology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 68:6241-50. 2008
    ..Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch...
  60. pmc Concentric zones of active RhoA and Cdc42 around single cell wounds
    Hélène A Benink
    Department of Zoology, University of Wisconsin Madison, Madison, WI 53706, USA
    J Cell Biol 168:429-39. 2005
    ..Each of the zones makes distinct contributions to the organization and function of the actomyosin wound array. We propose that similar rho activity zones control related processes such as cytokinesis...
  61. pmc Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL
    Raghuveer Singh Mali
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA
    Cancer Cell 20:357-69. 2011
    ..In summary we describe a pathway involving PI3K/Rho/ROCK/MLC that may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans...
  62. ncbi Impact of HMG CoA reductase inhibition on small GTPases in the heart
    Ulrich Laufs
    Medizinische Klinik und Poliklinik der Universität des Saarlandes, Innere Medizin III, 66421 Homburg Saar, Germany
    Cardiovasc Res 53:911-20. 2002
    ..Therefore, it was tested if these drugs inhibit Rac1 and RhoA activity in cardiomyocytes and, thereby, prevent angiotensin II-mediated expression of atrial natriuretic factor (ANF) and myosin light chain (MLC)-2 in the heart...
  63. ncbi Rho-kinase contributes to diphosphorylation of myosin II regulatory light chain in nonmuscle cells
    Kozue Ueda
    Department of Biological Science, Graduate School of Science, Hiroshima University, Higashi Hiroshima, 739 8526, Japan
    Oncogene 21:5852-60. 2002
    ..Taken together, it is suggested that Rho-kinase contributes to MRLC diphosphorylation and reorganization of actin filaments in nonmuscle cells...
  64. ncbi Yeast myosin light chain, Mlc1p, interacts with both IQGAP and class II myosin to effect cytokinesis
    J R Boyne
    Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, PO Box 594, Western Bank, Sheffield S10 2TN, UK
    J Cell Sci 113:4533-43. 2000
    ..It is proposed that Mlc1p therefore functions to recruit Iqg1p and in turn actin to the actomyosin ring and that it is also required for Myo1p function during ring contraction...
  65. doi Activation of Rho kinase isoforms in lung endothelial cells during inflammation
    Phyllus Y Mong
    The Tumor Immunology Laboratory, Division of Surgical Oncology, Department of Surgery, Columbia University, New York, NY 10032, USA
    J Immunol 182:2385-94. 2009
    ..Therefore, ROCK1 and ROCK2 are both activated by TNF-alpha and can be functionally separated in the signaling pathways leading to TNF-alpha-induced MLC phosphorylation and permeability increases...
  66. ncbi Differentiation and integrity of cardiac muscle cells are impaired in the absence of beta 1 integrin
    R Fassler
    Max Planck Institute of Biochemistry, Martinsried, Germany
    J Cell Sci 109:2989-99. 1996
    ..Thus, we conclude that interactions with the extracellular matrix via beta 1 integrin is necessary for differentiation and the maintenance of a specialized phenotype of cardiac muscle cells...
  67. ncbi Myosin phosphatase targeting subunit 1 affects cell migration by regulating myosin phosphorylation and actin assembly
    Donglan Xia
    Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9040, USA
    Exp Cell Res 304:506-17. 2005
    ..Proper expression of MYPT1 or variant 2 is critical for RLC phosphorylation and actin assembly, thus maintaining normal cellular functions by simultaneously controlling cytoskeletal architecture and actomyosin activation...
  68. ncbi Rho-binding kinase (LET-502) and myosin phosphatase (MEL-11) regulate cytokinesis in the early Caenorhabditis elegans embryo
    Alisa J Piekny
    Genes and Development Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
    J Cell Sci 115:2271-82. 2002
    ..Proteins including Rho GTPase activating protein/CYK-4 and late CYK-1, which are required for late stages of cytokinesis, function downstream of LET-502 and MEL-11...
  69. ncbi The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation
    J S Davis
    Molecular Physiology Section, Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 107:631-41. 2001
    ..To demonstrate the importance of cardiac light chain phosphorylation, we cloned a myosin light chain kinase from a human heart and have identified a gain-in-function mutation in two individuals with cardiac hypertrophy...
  70. ncbi Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization
    Ahmet Yildiz
    Center for Biophysics and Computational Biology, University of Illinois, Urbana Champaign, IL 61801, USA
    Science 300:2061-5. 2003
    ..These results strongly support a hand-over-hand model of motility, not an inchworm model...
  71. ncbi Phosphorylation of non-muscle myosin II regulatory light chain by p21-activated kinase (gamma-PAK)
    T L Chew
    Department of Pathology, St Louis University School of Medicine, Missouri 63104 1028, USA
    J Muscle Res Cell Motil 19:839-54. 1998
    ..Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization...
  72. ncbi The adapter protein CrkII regulates neuronal Wiskott-Aldrich syndrome protein, actin polymerization, and tension development during contractile stimulation of smooth muscle
    Dale D Tang
    Department of Cellular and Integrative Physiology, School of Medicine, Indiana University, Indianapolis, 46202, USA
    J Biol Chem 280:23380-9. 2005
    ..These studies suggest a novel signaling pathway for the regulation of N-WASp activation and active contraction in smooth muscle tissues...
  73. pmc Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway
    Yasuhiro Kidera
    Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi Osaka 577 8502, Japan
    J Exp Clin Cancer Res 29:127. 2010
    ..In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line...
  74. pmc Activation of aortic endothelial cells by oxidized phospholipids: a phosphoproteomic analysis
    Alejandro Zimman
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095 1770, USA
    J Proteome Res 9:2812-24. 2010
    ..Many changes in protein phosphorylation induced by Ox-PAPC are reported here for the first time and provide new insights into the mechanism of activation by oxidized lipids, including phosphorylation-based signal transduction...
  75. pmc The Rho kinases I and II regulate different aspects of myosin II activity
    Atsuko Yoneda
    Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, London SW7 2AZ, England, UK
    J Cell Biol 170:443-53. 2005
    ..ROCK II bound phosphatidylinositol 3,4,5P(3) and was sensitive to its levels, properties not shared by ROCK I. Therefore, endogenous ROCKs are distinctly regulated and in turn are involved with different myosin compartments...
  76. doi Direct evidence for roles of phosphorylated regulatory light chain of myosin II in furrow ingression during cytokinesis in HeLa cells
    Satoshi Asano
    Department of Biological Science, Graduate School of Science, Hiroshima University, Higashi Hiroshima 739 8526, Japan
    Genes Cells 14:555-68. 2009
    ..These results suggest that the P-MRLC is essential for the progress of furrow ingression but not the retainment of F-actin and myosin II in the contractile ring of dividing HeLa cells...
  77. doi Causes of fatigue in slow-twitch rat skeletal muscle during dynamic activity
    Morten Munkvik
    Institute for Experimental Medical Research, Oslo Univ Hospital, Ulleval, Kirkeveien 166, N 0407 Oslo, Norway
    Am J Physiol Regul Integr Comp Physiol 297:R900-10. 2009
    ..Although metabolic changes may account for the changes of F(max), -dF/dt, and V(0), dephosphorylation of MLC2s may be involved in the fatigue seen as sustained slower contraction velocities and decreased muscle shortening...
  78. ncbi Characterization of protein kinase pathways responsible for Ca2+ sensitization in rat ileal longitudinal smooth muscle
    Eikichi Ihara
    Smooth Muscle Research Group and Department of Biochemistry and Molecular Biology, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada
    Am J Physiol Gastrointest Liver Physiol 293:G699-710. 2007
    ..The negative regulation of MLCP by PKC and MAPKs during microcystin-induced contraction at pCa 9, which is not observed in vascular smooth muscle, may be unique to phasic smooth muscle...
  79. pmc Myosin light chain kinase activation and calcium sensitization in smooth muscle in vivo
    Yusuke Mizuno
    Dept Physiology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9040, USA
    Am J Physiol Cell Physiol 295:C358-64. 2008
    ..Thus the onset of agonist-induced contraction in phasic smooth muscle results from the rapid and coordinated activation of MLCK with hierarchical inhibition of MLCP by CPI-17 and MYPT1 phosphorylation...
  80. ncbi ROCK- and myosin-dependent matrix deformation enables protease-independent tumor-cell invasion in vivo
    Jeffrey B Wyckoff
    Analytical Imaging Facility, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Curr Biol 16:1515-23. 2006
    ..Imaging of live tumors shows that MLC is organized in a similar ROCK-dependent fashion in vivo and that inhibition of ROCK but not matrix-metalloproteases reduces cancer cell motility in vivo...
  81. pmc Distinct tissue distributions and subcellular localizations of differently phosphorylated forms of the myosin regulatory light chain in Drosophila
    Liang Zhang
    Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA
    Gene Expr Patterns 11:93-104. 2011
    ..These antibodies thus have the potential to be very useful in monitoring myosin activation for functional studies of morphogenesis in Drosophila...
  82. ncbi Phosphorylation of myosin regulatory light chain by myosin light chain kinase, and muscle contraction
    Seiji Takashima
    Departments of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan
    Circ J 73:208-13. 2009
    ..Therefore, I also review the differences in the connection between each MLCK and muscle contraction in the 3 muscle types...
  83. ncbi HeLa ZIP kinase induces diphosphorylation of myosin II regulatory light chain and reorganization of actin filaments in nonmuscle cells
    M Murata-Hori
    Department of Biological Science, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8526, Japan
    Oncogene 20:8175-83. 2001
    ..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...
  84. pmc Myosin regulatory light chain diphosphorylation slows relaxation of arterial smooth muscle
    Cindy Sutherland
    Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Biol Chem 287:24064-76. 2012
    ....
  85. ncbi Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions
    Patrik Verstreken
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
    Neuron 47:365-78. 2005
    ..Our data suggest a specific role for mitochondria in regulating synaptic strength...
  86. pmc The on-off switch in regulated myosins: different triggers but related mechanisms
    Daniel M Himmel
    Rosenstiel Basic Medical Sciences Research Center, Biology Department, Brandeis University, Waltham, MA 02453 2728, USA
    J Mol Biol 394:496-505. 2009
    ..We propose that disruption of critical links with the C-lobe of the RLC is the key event initiating the off-state in both smooth muscle myosins and molluscan myosins...
  87. pmc Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain
    Matthew P Josephson
    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
    Biochem Biophys Res Commun 416:367-71. 2011
    ....
  88. ncbi PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and cell chemotaxis
    Liron Even-Faitelson
    Department of Biochemistry, Institute of Medical Sciences, Faculty of Medicine, The Hebrew University, P O B 12272, Jerusalem 91120, Israel
    Cell Signal 17:1137-48. 2005
    ..Furthermore, the data presented here suggest that PAK1 plays a crucial role in the regulation of cell morphology and chemotaxis by regulating the phosphorylation and cellular localization of myosin II-B...
  89. pmc Differential roles of regulatory light chain and myosin binding protein-C phosphorylations in the modulation of cardiac force development
    Brett A Colson
    Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53711, USA
    J Physiol 588:981-93. 2010
    ....
  90. ncbi Myosin light chain 2 into the mainstream of cardiac development and contractility
    Richard L Moss
    Circ Res 99:225-7. 2006
  91. pmc Phosphorylated HSP20 modulates the association of thin-filament binding proteins: caldesmon with tropomyosin in colonic smooth muscle
    Sita Somara
    Gastrointestinal Molecular Motors Laboratory, Department of Pediatrics, Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan 48109 0658, USA
    Am J Physiol Gastrointest Liver Physiol 299:G1164-76. 2010
    ..We thus propose the crucial physiological relevance of molecular signaling switch (phosphorylation state of HSP27 and HSP20), which dictates 1) the phosphorylation states of TM and CaD and 2) their dissociations from each other...
  92. ncbi Intrathecal administration of Y-27632, a specific rho-associated kinase inhibitor, for rat neoplastic meningitis
    Hidemitsu Nakagawa
    Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1 3 3 Nakamichi, Higashinari ku, Osaka 537 8511, Japan
    Mol Cancer Res 3:425-33. 2005
    ..Taken together, our findings indicate that continuous intrathecal administration of Y-27632 could be a promising therapeutic method when combined with chemotherapy for treating human neoplastic meningitis...
  93. pmc Phosphorylation-dependent power output of transgenic flies: an integrated study
    M H Dickinson
    Department of Integrative Biology, University of California, Berkeley 94720, USA
    Biophys J 73:3122-34. 1997
    ..This behavioral alteration is not seen in another mutant strain in which the power output and estimated number of recruited cross-bridges is similar to that of wild type...
  94. pmc The molecular effects of skeletal muscle myosin regulatory light chain phosphorylation
    Michael J Greenberg
    Dept of Physiology and Biophysics, Boston Univ School of Medicine, 72 E Concord St, Boston, MA 02118, USA
    Am J Physiol Regul Integr Comp Physiol 297:R265-74. 2009
    ..Last, we showed that the duty cycle of skeletal muscle myosin is strain dependent, consistent with the notion that strain slows the rate of ADP release in striated muscle...
  95. ncbi Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy
    J Flavigny
    Biochimie B, and IFR de Physiopathologie et de Génétique Cardiovasculaire, Hopital Pitie Salpetriere, Paris, France
    J Mol Med (Berl) 76:208-14. 1998
    ..In 1996 two other genes encoding ventricular regulatory and essential myosin light chains were shown to be associated with a particular phenotype of the disease characterized by mid left ..
  96. pmc Inhibiting myosin light chain kinase induces apoptosis in vitro and in vivo
    Fabeha Fazal
    Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, Illinois 60612, USA
    Mol Cell Biol 25:6259-66. 2005
    ..Thus, MLC20 dephosphorylation occurs during physiological cell death and prolonged MLC20 dephosphorylation can trigger apoptosis...
  97. ncbi Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts
    J van der Velden
    Laboratory for Physiology, Department of Cardiology, Institute for Cardiovascular Research, Free University, Amsterdam, The Netherlands
    Circulation 104:1140-6. 2001
    ..We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca(2+), P(i), and pH...
  98. pmc Expression of CPI-17 and myosin phosphatase correlates with Ca(2+) sensitivity of protein kinase C-induced contraction in rabbit smooth muscle
    T P Woodsome
    Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA
    J Physiol 535:553-64. 2001
    ..This implicates CPI-17 inhibition of MLCP as an important component in modulating vascular muscle tone...
  99. ncbi Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton
    C G Winter
    Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA
    Cell 105:81-91. 2001
    ..Drosophila myosin VIIA, the homolog of the human Usher Syndrome 1B gene, also functions in conjunction with this newly defined portion of the Fz/Dsh signaling pathway to regulate the actin cytoskeleton...
  100. ncbi Enhanced skeletal muscle contraction with myosin light chain phosphorylation by a calmodulin-sensing kinase
    Jeffrey W Ryder
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    J Biol Chem 282:20447-54. 2007
    ..Importantly, RLC phosphorylation plays a prominent role in skeletal muscle force potentiation of fast-twitch type IIb but not type I or IIa fibers...
  101. ncbi Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction
    Z Wang
    Department of Cellular/Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Am J Respir Cell Mol Biol 25:628-35. 2001
    ..In summary, the data show that Rho-kinase is activated by hypoxia in PASMCs, and Rho/Rho-kinase is functionally linked to hypoxia-induced MLC phosphorylation and plays a role in the sustained phase of HPV...

Research Grants79

  1. Myosin ELC, a novel therapeutic target for FHC
    Danuta Szczesna-Cordary; Fiscal Year: 2013
    ..These studies will help to determine the role(s) of the ELC and the N-terminal cardiac specific ELC extension in the regulation of contractile force in healthy and FHC-diseased hearts. ..
  2. Structual and Calcium Regulatory Proteins in Sarcopenia
    LaDora V Thompson; Fiscal Year: 2012
    ..II fibers that cannot be explained by myosin isoform switching, suggesting that the regulatory proteins, myosin light chains, are involved. This proposal has two aims: AIM 1...
  3. LENGTH REGULATION OF CARDIAC CONTRACTION
    Donald Martyn; Fiscal Year: 2010
    ....
  4. The role of RhoA and its targets in craniofacial cartilage morphogenesis
    BARBARA SISSON; Fiscal Year: 2010
    ..in regulating the shape and behavior of chondrocytes and does so through Ppp1 r12a, an inhibitor of the myosin light chains. We will establish if Ppp1 r12a helps control chondrocyte behavior by determining if a genetic interaction ..
  5. CGMP DEPENDENT PROTEIN KINASE IN VASCULAR BIOLOGY
    HOWARD SURKS; Fiscal Year: 2003
    ..Contraction and relaxation of smooth muscle depend on the phosphorylation- dephosphorylation of myosin light chains by the myosin light chain kinase and myosin phosphatase (PP1M) respectively...
  6. ETIOLOGY AND DEVELOPMENT OF CONGENITAL HEART DISEASES
    Donald Patterson; Fiscal Year: 1999
    ..mitotic cells of the myocardium and cushion tissue of the embryonic heart, analysis of the distribution of myosin light chains in embryonic and fetal myocardium using protein gel electrophoresis (1D, 2D PAGE) and antibodies against ..
  7. EFFECT OF TSH ON THYROID METABOLISM
    WILLIAM DEERY; Fiscal Year: 1991
    ..with 32P, TSH rapidly caused a reduction of 32p in two polypeptides having many characteristics of myosin light chains (MLC)...
  8. MOLECULAR MECHANISM OF THE REGULATION IN SMOOTH MUSCLE
    Mitsuo Ikebe; Fiscal Year: 1991
    ..Second, the role of myosin light chains (20,000 dalton and 17,00 dalton) for the regulation of ATPase activity will be studied...
  9. MODULATORS OF MUSCLE CROSS-BRIDGE FUNCTION
    Roger Cooke; Fiscal Year: 2009
    ..Phosphorylation of myosin light chains disrupts the ordered array and its role in potentiating fiber tension will be explored in detail...
  10. CONTRACTILE PROTEIN EXPRESSION IN FAILING HUMAN HEART
    Michael Bristow; Fiscal Year: 2002
    ..abnormalities have been detected by our group and others in the mRNA and/or protein expression of MyHC, myosin light chains, and troponin T isoforms...
  11. MODULATION OF VASCULAR CONTRACTION BY PHOSPHATASES
    JOSEPH LASH; Fiscal Year: 1990
    ..the phosphatase activities in vascular smooth muscle which demonstrate activity toward isolated myosin light chains or intact myosin; 2) to classify myosin phosphatase activities with respect to other known substrates and ..
  12. MOLECULAR GENETIC ANALYSIS OF MOTILITY MYOSIN LCS
    Rex Chisholm; Fiscal Year: 2002
    ..The primary experimental approaches used in these studies include the molecular genetic manipulation of myosin light chains and the characterization of the consequences of these manipulations on the biochemistry, cellular ..
  13. ROLE OF MYOFILAMENT BOUND CALCIUM IN MUSCLE CONTRACTION
    MARIE CANTINO; Fiscal Year: 2003
    ..Modifications of myofibrillar protein composition will include extraction of TnC, myosin light chains and actin, and exchange of TnC isoforms (skeletal, cardiac or a mutant with modified Ca binding properties)...
  14. CELLULAR MECHANISMS REGULATING MYOMETRIAL FUNCTION
    James Stull; Fiscal Year: 1993
    ..properties of contraction will be established in relation to extents and sites of phosphorylation of myosin light chains, myosin heavy chains, caldesmon and myosin light chain kinase...
  15. Novel Role of Pre-B-Cell Colony Enhancing Factor in Acute Lung Injury (ALI)
    Shui Qing Ye; Fiscal Year: 2010
    ..endothelial cell transendothelial electric resistance, stress fiber formation, and phosphorylation of myosin light chains. Specific Aim 3 will define the signal transduction pathways of PBEF-mediated endothelial barrier ..
  16. STRUCTURE OF HUMAN CARDIAC MYOSIN LIGHT CHAIN GENES
    Satyapriya Sarkar; Fiscal Year: 1990
    ..studies indicate that the human ventricular light chains are indistinguishable from slow skeletal myosin light chains by several criteria...
  17. HUMAN SKELETAL MUSCLE MYOSIN ISOFORM IN HEALTH & DISEASE
    JUDITH SAWCHAK; Fiscal Year: 1990
    ..The McAbs will be generated using human skeletal myosin light chains as immunogen to BALB/C mice...
  18. Novel MLCK-MIF Interaction in Endothelium
    Ari Zaiman; Fiscal Year: 2002
    ..Our work has demonstrated a critical role of phosphorylation of myosin light chains (MLC) catalyzed by the Ca+2 - CaM dependent endothelial cell myosin light chain kinase (EC MLCK) in ..
  19. CALCIUM-CALMODULIN PROTEIN KINASE IN SEA URCHIN EGGS
    LIONEL REBHUN; Fiscal Year: 1990
    ..kinases of brain in that it will phosphorylate casein, sea urchin tubulin and brain MAP-2, in addition to myosin light chains. We will investigate the egg for other calcium dependent kinases and will develop antibodies to the kinases ..
  20. MUSCLE MATURATION: GROWTH FACTORS AND AGING
    Richard Strohman; Fiscal Year: 1990
    ..all of which show a transition from embryonic to adult isoform synthesis pattern, are myosin heavy chains, myosin light chains, tropomyosin and troponin. Regeneration will be studied in vivo with a cold-injury procedures...
  21. CONTROL OF CONTRACTION IN STRIATED MUSCLE
    ALBERT GORDON; Fiscal Year: 2000
    ..This will provide a more complete understanding of how muscle contraction is regulated, the central step in movement, and how movement itself affects regulation. ..
  22. DO LIGHT CHAIN EXTENSIONS ENHANCE MUSCLE POWER OUTPUT?
    David Maughan; Fiscal Year: 2004
    ..Enhanced oscillatory power output is correlated with the presence of extensions of the amino terminus of myosin light chains. Homologous extensions exist in myosin essential light chains of vertebrate myocardium and the regulatory ..
  23. MLC Dephosphorylation in Smooth Muscle Cell Apoptosis
    Fabeha Fazal; Fiscal Year: 2002
    ..First, myosin light chains are dephosphorylated during apoptosis; Second, the activity of myosin light chain kinase (MLCK), the enzyme ..
  24. Endothelial Cell Cytoskeletal Regulation by Cortactin
    Steven Dudek; Fiscal Year: 2006
    ..Recent work in endothelial cells (EC) demonstrates that phosphorylation of myosin light chains (MLC) by the enzyme myosin light chain kinase (MLCK) is critical to induction of vascular permeability in ..
  25. MOLECULAR ANGLE TRANSITIONS IN MUSCLE
    THOMAS BURGHARDT; Fiscal Year: 2001
    ....
  26. Single Muscle Fiber Contractile Properties With Aging
    Scott Trappe; Fiscal Year: 2005
    ..With this information we will be able to determine, for the first time, the interaction of aging, resistance training, and gender on single muscle fiber contractile function. ..
  27. Rotation of Single Cross-Bridge in Skeletal Muscle Fiber
    Julian Borejdo; Fiscal Year: 2007
    ..This is expected to provide definitive answers about the mechanism of contraction of skeletal muscle. ..
  28. Structural dynamics of myosin light chains
    Osha Roopnarine; Fiscal Year: 2008
    ..for muscle contraction, with specific emphasis on the functional dynamics of the skeletal and cardiac myosin light chains (LC) isoforms and their role in muscle disease...
  29. Improved Confocal Microscope: Detection & Functionality
    Julian Borejdo; Fiscal Year: 2005
    ..To facilitate a future commercialization, a microscope maintenance/modification company that is interested in distribution of the product version of the modification package has been identified. ..
  30. P20-Mediated Suppression of Vascular Force
    Christopher Rembold; Fiscal Year: 2004
    ..Many current treatments target smooth muscle to reduce tone. It is possible that targeting the force suppression pathway (i.e. p20) might provide comparable benefits. ..
  31. IMAGING MELANIN IN MELANOCYTES
    Julian Borejdo; Fiscal Year: 2003
    ..The modifications are relatively simple, inexpensive and not tied to a specific brand of instrument. It is expected that the method will find application in a small diagnostic laboratory. ..
  32. NO-CGMP INHIBITION OF UROGENITAL SMOOTH MUSCLE
    Christopher Rembold; Fiscal Year: 2004
    ....
  33. Mechanism of Ca2+ Sensitization in Smooth Muscle
    Toshio Kitazawa; Fiscal Year: 2006
    ..abstract_text> ..
  34. Role of Rho Kinase in Aqueous Humor Outflow Pathway
    P Rao; Fiscal Year: 2004
    ..Identification of specific signaling mechanisms regulating function of outflow pathway tissues could enable the design of target-specific approaches to the treatment of glaucoma. ..
  35. MECHANISMS OF ANESTHETIC ACTION ON SMOOTH MUSCLE
    JUDY SU; Fiscal Year: 2004
    ..Further the understanding of signal pathways of CaMKII and PKC in smooth muscle will advance understanding mechanisms of agonist-activated force maintenance in smooth muscle, as well as cell motility and migration in non-muscle cells. ..
  36. G PROTEIN MEDIATED CA++ SENSITIZATION IN SMOOTH MUSCLE
    Toshio Kitazawa; Fiscal Year: 2002
    ....
  37. Enteropathogenic E. coli Effects on Intestinal Function
    Gail A Hecht; Fiscal Year: 2010
    ..4. To evaluate the effect of EPEC infection on TJ structure and function in vivo using a mouse model and investigate the effector molecules and mechanisms involved. ..
  38. Fluorescence Lifetime and Steady-State Spectrometer
    E Ostap; Fiscal Year: 2003
    ..The core user group has extensive training in the operation, design, and maintenance of spectroscopic equipment. ..
  39. Olympus FV1000 Laser Scanning Confocal Microscope
    William Bement; Fiscal Year: 2007
    ..This information, in turn, will help guide future investigations of a number of normal and pathological human processes such as wound repair, nerve regeneration, cancer, and birth defects. [unreadable] [unreadable] [unreadable]..
  40. Zeiss Dynamic Laser TIRF
    Richard Minshall; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  41. Altered Glucose and Lipid Metabolism in Obesity and CVD
    MAUREEN CHARRON; Fiscal Year: 2007
    ....
  42. Regulation of Mammalian Class VI Myosin
    Mitsuo Ikebe; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  43. Leupeptin in a Canine Model of Duchenne Muscular Dystrophy
    MARTIN CHILDERS; Fiscal Year: 2006
    ..Specific Aim #4b: Compare lean body muscle mass and calpain activity between leupeptin and placebo-treated GRMD dogs. ..
  44. 17a-OH progesterone caproate and progesterone actions in human myometrial cells
    MELVYN SOLOFF; Fiscal Year: 2008
    ..Unraveling these intricate pathways is essential to understanding biological mechanisms that control myometrial function and could lead to the development of improved and/or novel tocolytics. [unreadable] [unreadable] [unreadable]..
  45. Protein Oxidation, Structure, & Function in Aging Muscle
    David Thomas; Fiscal Year: 2008
    ..abstract not provided ..
  46. Development of Diabetic Cardiomyopathy in GLUT4 +/- Mice
    MAUREEN CHARRON; Fiscal Year: 2004
    ..The latter studies will determine the mechanism of action of TZDs in the heart and may reveal novel therapeutic targets and applications. ..
  47. Purchase of a FEI Titan Krios for 3-D EM
    Kenneth Taylor; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  48. Solvent Modeling for HIV RT Drug Design
    Daniel Himmel; Fiscal Year: 2006
    ..The method may advance the field of macromolecular X-ray crystallography, opening up new opportunities for structure-based drug design to treat AIDS and a variety of other disorders. ..
  49. Caveolin-1 and NO Regulate PMN-mediated Increases in Vascular Permeability
    Richard D Minshall; Fiscal Year: 2011
    ....
  50. Myocilin-induced ER Stress in Trabecular Meshwork Cells
    SANGLY SRINIVAS; Fiscal Year: 2005
    ..These studies will lead to the development of an essential knowledge base and influence research in the field of glaucoma pathophysiology, diagnostics, and therapeutics. ..
  51. Multidisciplinary Study of Right Ventricular Dysplasia
    Jeffrey Towbin; Fiscal Year: 2005
    ..This integrated research grant proposal offers a substantial prospect of expanding the fund of clinical knowledge regarding ARVD and of localizing the gene(s) responsible for this disorder. ..
  52. PHYSIOLOGY AND PATHOLOGY OF SMOOTH MUSCLE HETEROGENEITY
    THOMAS EDDINGER; Fiscal Year: 2007
    ..4) SMC's found in the intimal thickening of an atherosclerotic vessel will differ in their myosin isoform expression and mechanical properties relative to the medial SMC's. [unreadable] [unreadable]..
  53. Mechanical Ventilation and Diaphragmatic Oxidant Injury
    Scott Powers; Fiscal Year: 2008
    ..abstract_text> ..
  54. ANESTHETIC REACTIONS IN SURGERY
    David Thomas; Fiscal Year: 2003
    ....
  55. MUSCLE RESPONSE TO STRESS IN CANINE MUSCULAR DYSTROPHY
    MARTIN CHILDERS; Fiscal Year: 2002
    ..It is anticipated that findings will improve the understanding of how dystrophic muscle responds to physical stress resulting in improved treatment for patients with Duchenne muscular dystrophy. ..
  56. NFAT and MEF-2 Choreograph Bladder Wall Remodeling Following Partial Outlet Obstr
    STEPHEN ANTHONY ZDERIC; Fiscal Year: 2010
    ..New therapy to preserve and enhance native bladder function will help avoid the development of the end stage bladder. ..
  57. MECHANOSENSITIVE MODULATION OF AIRWAY CONTRACTION
    Chi Ming Hai; Fiscal Year: 2008
    ..Understanding the basic science of this cellular mechanism may lead to new methods for the treatment of airway diseases such as asthma. ..
  58. MULTIVALENT VACCINE FOR LYMPHATIC FILARIASIS
    Ramaswamy Kalyanasundaram; Fiscal Year: 2010
    ..The proposed studies are based on solid preliminary data and are hypotheses driven. Results from these studies, we believe will advance our knowledge towards developing a defined vaccine against lymphatic filariasis in the human. ..
  59. Roles of Myosin Light Chain Kinases in the Heart
    James T Stull; Fiscal Year: 2010
    ..Results from these studies will provide novel biochemical insights into the physiological regulation and functional importance of cardiac myosin light chain phosphorylation. ..
  60. Regulation of vascular smooth muscle calcium sensitivity
    Paul H Ratz; Fiscal Year: 2010
    ..The Specific Aim of this study will be to test the hypothesis that ROK and PKCzeta both mediate KCI- induced Ca sensitization of FA, and that iPLA2 and PI3K are required as upstream activators of ROK and PKCzeta. ..
  61. CATCH: Mechanochemistry and Regulation in Smooth Muscle
    Thomas Butler; Fiscal Year: 2008
    ..4) Determination of the extent of involvement of myosin crossbridges in catch force maintenance by measurements of changes in orientation of fluorescent probes attached to the regulatory light chain. ..
  62. Regulation of p21waf1/cip1 by Rho and Ras signaling
    Michael Olson; Fiscal Year: 2008
    ..abstract_text> ..
  63. International Conference-Structural Mechanisms in Muscle
    Avril Somlyo; Fiscal Year: 2004
    ..Approaches include single-molecule nanotechnology, synchrotron radiation and the genetic basis of disease, all of which will be exemplified in the topics discussed at the conference. ..
  64. Purchase of a large format CCD camera for 3-D EM
    Kenneth Taylor; Fiscal Year: 2005
    ..The new instrumentation will allow for development of algorithms for increasing the area that can be reconstructed by electron tomography which may need corrections for focus gradient and for imaging distortions. ..
  65. Fibronectin mediated cell migration: signal integration
    Xiang Dong Ren; Fiscal Year: 2005
    ....
  66. MECHANICAL VENTILATION AND RESPIRATORY MUSCLES
    Scott Powers; Fiscal Year: 2004
    ..The long-term goal of our experiments is to provide the knowledge required to develop clinical strategies to oppose the deleterious effects of MV on respiratory muscles. ..
  67. IL-6 regulation of matrix degradation in liver fibrosis
    Meena Bansal; Fiscal Year: 2006
    ..Understanding these mechanisms will provide the basis for the development of novel anti-fibrotic therapies to treat a widely prevalent disease for which there is no effective treatment to date. ..
  68. High-Frequency Pulsed EPR Spectrometer
    David Thomas; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  69. Exercise, Antioxidants, and I-R Injury
    Scott Powers; Fiscal Year: 2006
    ..abstract_text> ..
  70. PEROXISOME PROLIFERATORS AND THE CELL CYCLE
    JANE ISHMAEL; Fiscal Year: 2002
    ..In general it is hoped that these studies will increase our understanding of the relationship between cell proliferation and hepatocarcinogenesis induced by nongenotoxic carcinogens. ..
  71. Regulation of Cardiac Glucose Transporters
    MAUREEN CHARRON; Fiscal Year: 2007
    ..Determining the role of GLUT8 in glucose metabolism and cardioprotection should provide novel insight into treatment of myocardial infarction and ischemic heart disease. [unreadable] [unreadable]..
  72. Motor Function and Regulation of Myosin VII
    Mitsuo Ikebe; Fiscal Year: 2007
    ..The proposed project will clarify the function and regulation of myosin VIIa, thus providing important information in understanding of the mechanism underlying the human sensory disorders of deafness and blindness. ..
  73. Function of Small G-Protein Binding Myosin
    Mitsuo Ikebe; Fiscal Year: 2007
    ..The proposed project will clarify the function and regulation of myosin IX, a unique member of myosin super family, thus provide a new insight into the mechanism of actin based motility. ..
  74. Myofibrillar Remodeling in Human Valvular Heart Disease:
    Peter VanBuren; Fiscal Year: 2007
    ..abstract_text> ..
  75. CONTRACTILE DYSFUNCTION IN ISCHEMIC HEART DISEASE
    Peter VanBuren; Fiscal Year: 2003
    ..Such data could ultimately be used to identify specific targets for interventions designed to confer protection. ..
  76. MYOD AND MYOGENIN IN MUSCLE HYPERTROPHY AND SARCOPENIA
    STEPHEN ALWAY; Fiscal Year: 2001
    ....
  77. MOLECULAR REGULATION OF SMOOTH MUSCLE ACTOMYOSIN
    Mitsuo Ikebe; Fiscal Year: 2004
    ..abstract_text> ..