Genomes and Genes
myosin light chains
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.
- Sheikh F, Ouyang K, Campbell S, Lyon R, Chuang J, Fitzsimons D, et al. Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease. J Clin Invest. 2012;122:1209-21 pubmed publisher..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. ..
- Kengyel A, Wolf W, Chisholm R, Sellers J. Nonmuscle myosin IIA with a GFP fused to the N-terminus of the regulatory light chain is regulated normally. J Muscle Res Cell Motil. 2010;31:163-70 pubmed publisher..These data indicate that despite some kinetic differences the N-terminal GFP fusion to the regulatory light chain is a reasonable model system for studying myosin function in vivo. ..
- Zhou G. The structural determinations of the leucine zipper coiled-coil domains of the cGMP-dependent protein kinase I? and its interaction with the myosin binding subunit of the myosin light chains phosphase. Protein Pept Lett. 2011;18:966-78 pubmed..It is intriguing to see that the successful incorporation of wenxiang diagrams and NMR spectroscopy in the LZCC structural and functional studies may provide some insights into protein-protein interaction mechanisms. ..
- Shiroguchi K, Chin H, Hannemann D, Muneyuki E, De La Cruz E, Kinosita K. Direct observation of the myosin Va recovery stroke that contributes to unidirectional stepping along actin. PLoS Biol. 2011;9:e1001031 pubmed publisher..Thus, the recovery stroke contributes to unidirectional stepping of myosin Va. ..
- England J, Loughna S. Heavy and light roles: myosin in the morphogenesis of the heart. Cell Mol Life Sci. 2013;70:1221-39 pubmed publisher..The human molecular genetics of the myosins will also be reviewed. ..
- Stull J, Kamm K, Vandenboom R. Myosin light chain kinase and the role of myosin light chain phosphorylation in skeletal muscle. Arch Biochem Biophys. 2011;510:120-8 pubmed publisher..Moreover, RLC phosphorylation-mediated enhancements may interact with neural strategies for human skeletal muscle activation to ameliorate either central or peripheral aspects of fatigue. ..
- Ding P, Huang J, Battiprolu P, Hill J, Kamm K, Stull J. Cardiac myosin light chain kinase is necessary for myosin regulatory light chain phosphorylation and cardiac performance in vivo. J Biol Chem. 2010;285:40819-29 pubmed publisher..Thus, cMLCK appears to be the predominant protein kinase that maintains basal RLC phosphorylation that is required for normal physiological cardiac performance in vivo. ..
- Kidera Y, Tsubaki M, Yamazoe Y, Shoji K, Nakamura H, Ogaki M, et al. 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. J Exp Clin Cancer Res. 2010;29:127 pubmed publisher..In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line...
- Wu Q, Sahasrabudhe R, Luo L, Lewis D, Gollin S, Saunders W. Deficiency in myosin light-chain phosphorylation causes cytokinesis failure and multipolarity in cancer cells. Oncogene. 2010;29:4183-93 pubmed publisher..These results for the first time define the molecular defects leading to divisional failure in cancer cells. ..
- Cho Y, Ahn D, Morgan K, Lee Y. Enhanced contractility and myosin phosphorylation induced by Ca(2+)-independent MLCK activity in hypertensive rats. Cardiovasc Res. 2011;91:162-70 pubmed publisher..0. Our results suggest that Ca(2+)-independent MLCK activity is enhanced in the SHR, and that ZIPK plays, at least in part, an important role as a candidate for this kinase in rat mesenteric arteries. ..
- Qi H, Wang P, Liu C, Li M, Wang S, Huang Y, et al. Involvement of HIF-1? in MLCK-dependent endothelial barrier dysfunction in hypoxia. Cell Physiol Biochem. 2011;27:251-62 pubmed publisher..The results suggest that HIF-1? is involved in the MLCK-dependent endothelial barrier dysfunction induced by hypoxia. ..
- Zhang L, Ward R. Distinct tissue distributions and subcellular localizations of differently phosphorylated forms of the myosin regulatory light chain in Drosophila. Gene Expr Patterns. 2011;11:93-104 pubmed publisher..These antibodies thus have the potential to be very useful in monitoring myosin activation for functional studies of morphogenesis in Drosophila. ..
- Greenberg M, Kazmierczak K, Szczesna Cordary D, Moore J. Cardiomyopathy-linked myosin regulatory light chain mutations disrupt myosin strain-dependent biochemistry. Proc Natl Acad Sci U S A. 2010;107:17403-8 pubmed publisher..We propose that the R58Q and N47K mutations alter the mechanical properties of the myosin neck region, leading to altered load-dependent kinetics that may explain the observed mutant-induced FHC phenotypes. ..
- Muthu P, Kazmierczak K, Jones M, Szczesna Cordary D. The effect of myosin RLC phosphorylation in normal and cardiomyopathic mouse hearts. J Cell Mol Med. 2012;16:911-9 pubmed publisher..Further studies are necessary to elucidate the mechanism of this unexpected phosphorylation-induced decrease in maximal tension in Tg-D166V-skinned muscle fibres. ..
- Somara S, Gilmont R, Varadarajan S, Bitar K. Phosphorylated HSP20 modulates the association of thin-filament binding proteins: caldesmon with tropomyosin in colonic smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2010;299:G1164-76 pubmed publisher..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. ..
- Liu H, Li M, Wang P, Wang F. Blockade of hypoxia-inducible factor-1? by YC-1 attenuates interferon-? and tumor necrosis factor-?-induced intestinal epithelial barrier dysfunction. Cytokine. 2011;56:581-8 pubmed publisher..YC-1 may be a potential agent for treatment of intestinal barrier disruption in inflammation...
- Mali R, Ramdas B, Ma P, Shi J, Munugalavadla V, Sims E, et al. Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL. Cancer Cell. 2011;20:357-69 pubmed publisher..In summary we describe a pathway involving PI3K/Rho/ROCK/MLC that may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans. ..
- Li R, Martin M, Liu Y, Wang B, Patel R, Zhu J, et al. Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors. J Med Chem. 2012;55:2474-8 pubmed publisher..Compounds 18 and 24 inhibited potently the phosphorylation of the ROCK substrate MLC2 in intact human breast cancer cells. ..
- Chen C, Wang P, Su Q, Wang S, Wang F. Myosin light chain kinase mediates intestinal barrier disruption following burn injury. PLoS ONE. 2012;7:e34946 pubmed publisher..It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. ..
- He W, Qiao Y, Zhang C, Peng Y, Chen C, Wang P, et al. Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension. Am J Physiol Heart Circ Physiol. 2011;301:H584-91 pubmed publisher..These results suggest that MLCK is necessary for both physiological and pathological blood pressure. MLCK(SMKO) mice may be a useful model of vascular failure and hypotension. ..
- Aslam M, Härtel F, Arshad M, Gündüz D, Abdallah Y, Sauer H, et al. cAMP/PKA antagonizes thrombin-induced inactivation of endothelial myosin light chain phosphatase: role of CPI-17. Cardiovasc Res. 2010;87:375-84 pubmed publisher..The permeability-lowering effect of the cAMP/Epac pathway is independent of CPI-17. ..
- Jacques A, Briceno N, Messer A, Gallon C, Jalilzadeh S, Garcia E, et al. The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy. Cardiovasc Res. 2008;79:481-91 pubmed publisher..The presence of a myosin heavy chain mutation causing hypertrophic cardiomyopathy can be predicted from a simple functional assay. ..
- Chang Y, Nalbant P, Birkenfeld J, Chang Z, Bokoch G. GEF-H1 couples nocodazole-induced microtubule disassembly to cell contractility via RhoA. Mol Biol Cell. 2008;19:2147-53 pubmed publisher..Conversely, RhoA activation and contractility are rescued by reintroduction of siRNA-resistant GEF-H1. Our studies reveal a critical role for a GEF-H1/RhoA/ROCK/MLC signaling pathway in mediating nocodazole-induced cell contractility. ..
- Wroblewski L, Shen L, Ogden S, Romero Gallo J, Lapierre L, Israel D, et al. Helicobacter pylori dysregulation of gastric epithelial tight junctions by urease-mediated myosin II activation. Gastroenterology. 2009;136:236-46 pubmed publisher..This process requires functional urease activity and is independent of the cag pathogenicity island or VacA. These data provide new insights into the mechanisms by which H pylori disrupts gastric barrier function. ..
- Barkan D, Kleinman H, Simmons J, Asmussen H, Kamaraju A, Hoenorhoff M, et al. Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Res. 2008;68:6241-50 pubmed publisher..Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch. ..
- He W, Peng Y, Zhang W, Lv N, Tang J, Chen C, et al. Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice. Gastroenterology. 2008;135:610-20 pubmed publisher..MLCK and its phosphorylation of RLC are required physiologically for smooth muscle contraction and are essential for normal gastrointestinal motility. ..
- Bultot L, Horman S, Neumann D, Walsh M, Hue L, Rider M. Myosin light chains are not a physiological substrate of AMPK in the control of cell structure changes. FEBS Lett. 2009;583:25-8 pubmed publisher..Therefore, MLC phosphorylation during energy deprivation does not result from direct phosphorylation by AMPK. ..
- Wang Y, Zheng X, Riddick N, Bryden M, Baur W, Zhang X, et al. ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res. 2009;104:531-40 pubmed publisher..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. ..
- Chang A, Chen G, Gerard R, Kamm K, Stull J. Cardiac myosin is a substrate for zipper-interacting protein kinase (ZIPK). J Biol Chem. 2010;285:5122-6 pubmed publisher..Knockdown of ZIPK in cardiac myocytes by small interfering RNA significantly decreased the extent of RLC Ser-15 phosphorylation. Thus, ZIPK may act as a cardiac RLC kinase and thereby affect contractility. ..
- Takashima S. Phosphorylation of myosin regulatory light chain by myosin light chain kinase, and muscle contraction. Circ J. 2009;73:208-13 pubmed..Therefore, I also review the differences in the connection between each MLCK and muscle contraction in the 3 muscle types. ..
- Tully G, Nishihama R, Pringle J, Morgan D. The anaphase-promoting complex promotes actomyosin-ring disassembly during cytokinesis in yeast. Mol Biol Cell. 2009;20:1201-12 pubmed publisher..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. ..
- Asano S, Hamao K, Hosoya H. Direct evidence for roles of phosphorylated regulatory light chain of myosin II in furrow ingression during cytokinesis in HeLa cells. Genes Cells. 2009;14:555-68 pubmed publisher..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. ..
- Greenberg M, Mealy T, Watt J, Jones M, Szczesna Cordary D, Moore J. The molecular effects of skeletal muscle myosin regulatory light chain phosphorylation. Am J Physiol Regul Integr Comp Physiol. 2009;297:R265-74 pubmed publisher..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...
- Himmel D, Mui S, O Neall Hennessey E, Szent Györgyi A, Cohen C. The on-off switch in regulated myosins: different triggers but related mechanisms. J Mol Biol. 2009;394:496-505 pubmed publisher..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. ..
- Gilles L, Bluteau D, Boukour S, Chang Y, Zhang Y, Robert T, et al. MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9. Blood. 2009;114:4221-32 pubmed publisher..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. ..
- Mizutani H, Okamoto R, Moriki N, Konishi K, Taniguchi M, Fujita S, et al. Overexpression of myosin phosphatase reduces Ca(2+) sensitivity of contraction and impairs cardiac function. Circ J. 2010;74:120-8 pubmed..Thus, MYPT2 is truly the regulatory subunit of cardiac MP in-vivo and plays a significant role in modulating cardiac function. (Circ J 2010; 74: 120 - 128). ..
- Zimman A, Chen S, Komisopoulou E, Titz B, Martinez Pinna R, Kafi A, et al. Activation of aortic endothelial cells by oxidized phospholipids: a phosphoproteomic analysis. J Proteome Res. 2010;9:2812-24 pubmed publisher..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. ..
- Aguilar H, Zielnik B, Tracey C, Mitchell B. Quantification of rapid Myosin regulatory light chain phosphorylation using high-throughput in-cell Western assays: comparison to Western immunoblots. PLoS ONE. 2010;5:e9965 pubmed publisher..However, the drawbacks of ICW include the need for a cell culture format and the lack of utility where protein purification, concentration or stoichiometric analyses are required. ..
- Cho T, Jung Y, Koschinsky M. 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. J Biol Chem. 2008;283:30503-12 pubmed publisher..Studies are ongoing to further dissect the molecular basis of these findings. ..
- Chan J, Takeda M, Briggs L, Graham M, Lu J, Horikoshi N, et al. Identification of cardiac-specific myosin light chain kinase. Circ Res. 2008;102:571-80 pubmed publisher..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. ..
- Christopher B, Pizarro G, Nicholson B, Yuen S, Hoit B, Ogut O. Reduced force production during low blood flow to the heart correlates with altered troponin I phosphorylation. J Muscle Res Cell Motil. 2009;30:111-23 pubmed publisher..These findings suggest that altered TnI function, due to changes in the distribution of phosphorylated sites, is an early contributor to reduced contractility of the heart. ..