Myl2

Summary

Gene Symbol: Myl2
Description: myosin, light polypeptide 2, regulatory, cardiac, slow
Alias: MLC-2, MLC-2s/v, MLC-2v, Mlc2v, Mylpc, myosin regulatory light chain 2, ventricular/cardiac muscle isoform, myosin light chain 2, slow skeletal/ventricular muscle isoform, myosin light chain 2v, myosin light chain, phosphorylatable, cardiac ventricles
Species: mouse
Products:     Myl2

Top Publications

  1. Kubalak S, Miller Hance W, O Brien T, Dyson E, Chien K. Chamber specification of atrial myosin light chain-2 expression precedes septation during murine cardiogenesis. J Biol Chem. 1994;269:16961-70 pubmed
    ..The region-specific expression of the MLC-2a and MLC-2v genes in their respective chambers during early cardiogenesis provides genetic markers for chamber specification (atrial and ventricular) in both the in vitro and in vivo context. ..
  2. Chen J, Kubalak S, Minamisawa S, Price R, Becker K, Hickey R, et al. Selective requirement of myosin light chain 2v in embryonic heart function. J Biol Chem. 1998;273:1252-6 pubmed
    ..O'Brien, T. X., and Evans, S. M. (1993) Annu. Rev. Physiol. 55, 77-95). We have disrupted myosin light chain 2v gene in mice and monitored in vivo cardiac function in living myosin light chain 2v -/- embryos...
  3. Chen H, Shi S, Acosta L, Li W, Lu J, Bao S, et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development. 2004;131:2219-31 pubmed
    ..This may provide an underlying mechanism for understanding the pathogenesis of both structural and functional congenital heart defects. ..
  4. Wang Z, Zhai W, Richardson J, Olson E, Meneses J, Firpo M, et al. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation. Genes Dev. 2004;18:3106-16 pubmed
    ..Importantly, BAF180 is recruited to the promoter of these target genes and BAF180 deficiency affects the RA response for CRABPII and RARbeta2. These studies reveal unique functions of PBAF in cardiac chamber maturation. ..
  5. Chen J, Kubalak S, Chien K. Ventricular muscle-restricted targeting of the RXRalpha gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis. Development. 1998;125:1943-9 pubmed
    ..transgenic artifacts, we employed a knock-in strategy to place cre recombinase coding sequences into the myosin light chain 2v (MLC2v) genomic locus, a gene which in the heart is expressed exclusively in ventricular cardiomyocytes at ..
  6. Cai C, Liang X, Shi Y, Chu P, Pfaff S, Chen J, et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003;5:877-89 pubmed
    ..Our results have implications for the development of specific cardiac lineages, left-right asymmetry, cardiac evolution, and isolation of cardiac progenitor cells. ..
  7. Henderson S, Goldhaber J, So J, Han T, Motter C, Ngo A, et al. Functional adult myocardium in the absence of Na+-Ca2+ exchange: cardiac-specific knockout of NCX1. Circ Res. 2004;95:604-11 pubmed
    ..The magnitude of Ca2+ transients appears to be maintained by an increased gain of sarcoplasmic reticular Ca2+ release. The myocardium of the NCX1 knockout mice undergoes a remarkable adaptation to maintain near normal cardiac function. ..
  8. Koushik S, Bundy J, Conway S. Sodium-calcium exchanger is initially expressed in a heart-restricted pattern within the early mouse embryo. Mech Dev. 1999;88:119-22 pubmed
    ..However, in more developed embryos (11.0 dpc and older) NCX1 is expressed in other tissues. ..
  9. Sanbe A, Fewell J, Gulick J, Osinska H, Lorenz J, Hall D, et al. Abnormal cardiac structure and function in mice expressing nonphosphorylatable cardiac regulatory myosin light chain 2. J Biol Chem. 1999;274:21085-94 pubmed
    ..We conclude that regulated phosphorylation of the regulatory myosin light chains appears to play an important role in maintaining normal cardiac function over the lifetime of the animal. ..

More Information

Publications62

  1. Phillips H, Hildreth V, Peat J, Murdoch J, Kobayashi K, Chaudhry B, et al. Non-cell-autonomous roles for the planar cell polarity gene Vangl2 in development of the coronary circulation. Circ Res. 2008;102:615-23 pubmed publisher
    ..These data suggest that Vangl2 and Rho kinase act cell autonomously in the myocardium to regulate the organization of cardiomyocytes but also have non-cell-autonomous effects on the formation of the coronary vasculature. ..
  2. Roux M, Laforest B, Capecchi M, Bertrand N, Zaffran S. Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development. Dev Biol. 2015;406:247-58 pubmed publisher
    ..Our findings provide new insights into the gene regulatory network controlling SHF and OFT formation. ..
  3. Ling H, Gray C, Zambon A, Grimm M, Gu Y, Dalton N, et al. Ca2+/Calmodulin-dependent protein kinase II ? mediates myocardial ischemia/reperfusion injury through nuclear factor-?B. Circ Res. 2013;112:935-44 pubmed publisher
  4. Liberatore C, Searcy Schrick R, Yutzey K. Ventricular expression of tbx5 inhibits normal heart chamber development. Dev Biol. 2000;223:169-80 pubmed
    ..These studies provide direct evidence for an essential role for tbx5 in early heart morphogenesis and chamber-specific gene expression. ..
  5. Nakajima K, Inagawa M, Uchida C, Okada K, Tane S, Kojima M, et al. Coordinated regulation of differentiation and proliferation of embryonic cardiomyocytes by a jumonji (Jarid2)-cyclin D1 pathway. Development. 2011;138:1771-82 pubmed publisher
    ..Thus, a Jmj-cyclin D1 pathway coordinately regulates proliferation and differentiation of cardiomyocytes. ..
  6. Huang Y, Hickey R, Yeh J, Liu D, Dadak A, Young L, et al. Cardiac myocyte-specific HIF-1alpha deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart. FASEB J. 2004;18:1138-40 pubmed
    ..Further elucidating these relationships may help clarify the molecular pathology of various cardiovascular disease states, including ischemic cardiomyopathy and myocardial hibernation (5, 6). ..
  7. Cai C, Zhou W, Yang L, Bu L, Qyang Y, Zhang X, et al. T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis. Development. 2005;132:2475-87 pubmed
  8. Bruneau B, Bao Z, Tanaka M, Schott J, Izumo S, Cepko C, et al. Cardiac expression of the ventricle-specific homeobox gene Irx4 is modulated by Nkx2-5 and dHand. Dev Biol. 2000;217:266-77 pubmed
    ..These data indicate that the homeobox gene Irx4 is likely to be an important mediator of ventricular differentiation during cardiac development, which is downstream of Nkx2-5 and dHand. ..
  9. Duan X, Liu J, Zhu C, Wang Q, Cui X, Kim N, et al. RhoA-mediated MLC2 regulates actin dynamics for cytokinesis in meiosis. Cell Cycle. 2016;15:471-7 pubmed publisher
    ..Above all, our data indicated that the RhoA-mediated MLC2 regulates the actin organization for cytokinesis during mouse oocyte maturation. ..
  10. Christoffels V, Habets P, Franco D, Campione M, de Jong F, Lamers W, et al. Chamber formation and morphogenesis in the developing mammalian heart. Dev Biol. 2000;223:266-78 pubmed
    ..of genes encoding atrial natriuretic factor, sarcoplasmic reticulum calcium ATPase, Chisel, Irx5, Irx4, myosin light chain 2v, and beta-myosin heavy chain and related these to morphogenesis...
  11. Harmelink C, Peng Y, Debenedittis P, Chen H, Shou W, Jiao K. Myocardial Mycn is essential for mouse ventricular wall morphogenesis. Dev Biol. 2013;373:53-63 pubmed publisher
    ..In summary, Mycn acts downstream of BMP and NRG1 cardiogenic signaling pathways to promote normal myocardial wall morphogenesis. ..
  12. Khandekar A, Springer S, Wang W, HICKS S, Weinheimer C, Diaz Trelles R, et al. Notch-Mediated Epigenetic Regulation of Voltage-Gated Potassium Currents. Circ Res. 2016;119:1324-1338 pubmed publisher
    ..In summary, these findings demonstrate a novel mechanism for regulation of voltage-gated potassium currents in the setting of cardiac pathology and may provide a novel target for arrhythmia drug design. ..
  13. Lai Y, Su C, Jiang S, Chang Y, Lai A, Huang Y. Deficiency of CPEB2-Confined Choline Acetyltransferase Expression in the Dorsal Motor Nucleus of Vagus Causes Hyperactivated Parasympathetic Signaling-Associated Bronchoconstriction. J Neurosci. 2016;36:12661-12676 pubmed
    ..e., choline acetyltransferase). Consequently, increased parasympathetic signaling leads to hyperactivated bronchoconstriction and abnormal respiration in the KO neonates. ..
  14. Vanderlaan R, Hardy W, Kabir M, Pasculescu A, Jones N, DeTombe P, et al. The ShcA phosphotyrosine docking protein uses distinct mechanisms to regulate myocyte and global heart function. Circ Res. 2011;108:184-93 pubmed publisher
    ..In addition, analysis of the SH2 domain and CH1 pTyr sites reveals that ShcA mediates pTyr signaling in the adult heart through multiple distinct signaling elements that control myocardial functions and response to stresses. ..
  15. Hölscher M, Silter M, Krull S, von Ahlen M, Hesse A, Schwartz P, et al. Cardiomyocyte-specific prolyl-4-hydroxylase domain 2 knock out protects from acute myocardial ischemic injury. J Biol Chem. 2011;286:11185-94 pubmed publisher
    ..This correlated with a decreased number of apoptotic cells in the infarcted myocardium in the cPhd2(-/-) mice and significantly improved cardiac function 3 weeks after myocardial infarction. ..
  16. von Gise A, Lin Z, Schlegelmilch K, Honor L, Pan G, Buck J, et al. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci U S A. 2012;109:2394-9 pubmed publisher
    ..Activation of Yap1 in postnatal cardiomyocytes may be a useful strategy to stimulate cardiomyocyte expansion in therapeutic myocardial regeneration. ..
  17. Liao P, Georgakopoulos D, Kovacs A, Zheng M, Lerner D, Pu H, et al. The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. Proc Natl Acad Sci U S A. 2001;98:12283-8 pubmed
  18. Takeuchi T, Kojima M, Nakajima K, Kondo S. jumonji gene is essential for the neurulation and cardiac development of mouse embryos with a C3H/He background. Mech Dev. 1999;86:29-38 pubmed
  19. Komatsu Y, Shibuya H, Takeda N, Ninomiya Tsuji J, Yasui T, Miyado K, et al. Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis. Mech Dev. 2002;119:239-49 pubmed
    ..These results indicate a possibility that TAB1 plays an important role in mammalian embryogenesis and is required for TAK1 activation in TGF-beta signaling. ..
  20. Grego Bessa J, Bloomekatz J, Castel P, Omelchenko T, Baselga J, Anderson K. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium. elife. 2016;5:e12034 pubmed publisher
    ..The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis. ..
  21. Imahashi K, Pott C, Goldhaber J, Steenbergen C, Philipson K, Murphy E. Cardiac-specific ablation of the Na+-Ca2+ exchanger confers protection against ischemia/reperfusion injury. Circ Res. 2005;97:916-21 pubmed
    ..Thus, NCX-KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that Ca2+ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury. ..
  22. Togi K, Kawamoto T, Yamauchi R, Yoshida Y, Kita T, Tanaka M. Role of Hand1/eHAND in the dorso-ventral patterning and interventricular septum formation in the embryonic heart. Mol Cell Biol. 2004;24:4627-35 pubmed
    ..formation, we generated Hand1/eHAND knock-in mice where Hand1/eHAND cDNA was placed under the control of the MLC2V promoter...
  23. Zhao T, Huang X, Han L, Wang X, Cheng H, Zhao Y, et al. Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes. J Biol Chem. 2012;287:23615-25 pubmed publisher
  24. Constam D, Robertson E. SPC4/PACE4 regulates a TGFbeta signaling network during axis formation. Genes Dev. 2000;14:1146-55 pubmed
    ..These findings establish an important role for SPC4 in patterning the early mouse embryo. ..
  25. Amann R, Wyder S, Slavotinek A, Trueb B. The FgfrL1 receptor is required for development of slow muscle fibers. Dev Biol. 2014;394:228-41 pubmed publisher
    ..5 as indicated by the absence of slow fiber markers Myh7, Myl2 and Myl3...
  26. Kubalak S, Hutson D, Scott K, Shannon R. Elevated transforming growth factor beta2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor alpha knockout embryos. Development. 2002;129:733-46 pubmed
  27. Ramsbottom S, Sharma V, Rhee H, Eley L, Phillips H, Rigby H, et al. Vangl2-regulated polarisation of second heart field-derived cells is required for outflow tract lengthening during cardiac development. PLoS Genet. 2014;10:e1004871 pubmed publisher
    ..Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis. ..
  28. Lee M, Sun B, Schliffke S, Yue Z, Ye M, Paavola J, et al. Derivation of functional ventricular cardiomyocytes using endogenous promoter sequence from murine embryonic stem cells. Stem Cell Res. 2012;8:49-57 pubmed publisher
    ..By crossing the myosin light chain 2v (Mlc2v)-Cre mouse line with the reporter strain Rosa26-yellow fluorescent protein (YFP), we generated mESC ..
  29. Liu W, Zi M, Naumann R, Ulm S, Jin J, Taglieri D, et al. Pak1 as a novel therapeutic target for antihypertrophic treatment in the heart. Circulation. 2011;124:2702-15 pubmed publisher
    ..These results, for the first time, establish Pak1 as a novel antihypertrophic regulator and suggest that it may be a potential therapeutic target for the treatment of cardiac hypertrophy and heart failure. ..
  30. Lai K, Pawson T. The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo. Genes Dev. 2000;14:1132-45 pubmed
    ..ShcA may therefore orchestrate complex interactions within the vascular compartment by rendering cells permissive to respond to soluble and adhesive external cues. ..
  31. Wang X, Merritt A, Seyfried J, Guo C, Papadakis E, Finegan K, et al. Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway. Mol Cell Biol. 2005;25:336-45 pubmed
    ..Overall, this is the first study to rigorously establish the role of MEK5 in vivo as an activator of ERK5 and as an essential regulator of cell survival that is required for normal embryonic development. ..
  32. Agarwal U, Ghalayini W, Dong F, Weber K, Zou Y, Rabbany S, et al. Role of cardiac myocyte CXCR4 expression in development and left ventricular remodeling after acute myocardial infarction. Circ Res. 2010;107:667-76 pubmed publisher
    ..strains of CM-CXCR4(flox/flox) mice were generated by crossing CXCR4(flox/flox) mice with MCM-Cre(+/-) mouse and MLC2v-Cre(+/-) mouse on the C57BL/6J background, yielding CXCR4(flox/flox) MCM-Cre(+/-) and CXCR4(flox/flox)MLC2v-Cre(+/-..
  33. Yamagishi H, Yamagishi C, Nakagawa O, Harvey R, Olson E, Srivastava D. The combinatorial activities of Nkx2.5 and dHAND are essential for cardiac ventricle formation. Dev Biol. 2001;239:190-203 pubmed
    ..5 and dHAND. These studies provide the first demonstration of gene mutations that result in ablation of the entire ventricular segment of the mammalian heart, and reveal essential transcriptional pathways for ventricular formation. ..
  34. Lee K, Ross R, Rockman H, Harris A, O Brien T, Van Bilsen M, et al. Myosin light chain-2 luciferase transgenic mice reveal distinct regulatory programs for cardiac and skeletal muscle-specific expression of a single contractile protein gene. J Biol Chem. 1992;267:15875-85 pubmed
  35. Wakimoto K, Fujimura H, Iwamoto T, Oka T, Kobayashi K, Kita S, et al. Na+/Ca2+ exchanger-deficient mice have disorganized myofibrils and swollen mitochondria in cardiomyocytes. Comp Biochem Physiol B Biochem Mol Biol. 2003;135:9-15 pubmed
    ..Although NCX1 protein levels were decreased in heterozygous mice, there were no changes in NCX2 and NCX3 protein levels between wild type and heterozygous mice. ..
  36. Lee Y, Song A, Baker R, Micales B, Conway S, Lyons G. Jumonji, a nuclear protein that is necessary for normal heart development. Circ Res. 2000;86:932-8 pubmed
    ..These data demonstrate that JMJ is a nuclear protein, which is essential for normal heart development and function. ..
  37. Doroszko A, Polewicz D, Cadete V, Sawicka J, Jones M, Szczesna Cordary D, et al. Neonatal asphyxia induces the nitration of cardiac myosin light chain 2 that is associated with cardiac systolic dysfunction. Shock. 2010;34:592-600 pubmed publisher
    ..Inhibition of MLC2 nitration and/or direct inhibition of its degradation by MMP-2 could be potential therapeutic targets aiming at reduction of myocardial damage during resuscitation of asphyxiated newborns. ..
  38. Li P, Cavallero S, Gu Y, Chen T, Hughes J, Hassan A, et al. IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development. Development. 2011;138:1795-805 pubmed publisher
    ..5, concurrent with the establishment of coronary circulation. Our results define IGF2 as a previously unexplored epicardial mitogen that is required for normal ventricular chamber development. ..
  39. Ozcelik C, Erdmann B, Pilz B, Wettschureck N, Britsch S, Hubner N, et al. Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Proc Natl Acad Sci U S A. 2002;99:8880-5 pubmed
    ..In particular, they will allow a rigorous assessment of the role of ErbB2 in the heart and provide insight into the molecular mechanisms that underlie the adverse effects of anti-ErbB2 antibodies. ..
  40. Tanaka M, Schinke M, Liao H, Yamasaki N, Izumo S. Nkx2.5 and Nkx2.6, homologs of Drosophila tinman, are required for development of the pharynx. Mol Cell Biol. 2001;21:4391-8 pubmed
    ..Furthermore, the development of the atrium was less advanced in the double-mutant embryos, indicating that these two genes are essential for both pharyngeal and cardiac development. ..
  41. Franco D, Markman M, Wagenaar G, Ya J, Lamers W, Moorman A. Myosin light chain 2a and 2v identifies the embryonic outflow tract myocardium in the developing rodent heart. Anat Rec. 1999;254:135-46 pubmed
    ..b>MLC2v is strongly expressed in the ventricular myocardium and distinctly lower in the outflow tract and atrioventricular ..
  42. DiMichele L, Hakim Z, Sayers R, Rojas M, Schwartz R, Mack C, et al. Transient expression of FRNK reveals stage-specific requirement for focal adhesion kinase activity in cardiac growth. Circ Res. 2009;104:1201-8 pubmed publisher
    ..These findings indicate that dynamic expression of FRNK in the neonatal heart may function to promote cardiomyocyte quiescence in an environment that is particularly rich in growth factors and growth promoting extracellular matrices. ..
  43. Chuva de Sousa Lopes S, Hassink R, Feijen A, van Rooijen M, Doevendans P, Tertoolen L, et al. Patterning the heart, a template for human cardiomyocyte development. Dev Dyn. 2006;235:1994-2002 pubmed
  44. VONG L, Ragusa M, Schwarz J. Generation of conditional Mef2cloxP/loxP mice for temporal- and tissue-specific analyses. Genesis. 2005;43:43-8 pubmed
  45. Ding J, Xu X, Yang D, Chu P, Dalton N, Ye Z, et al. Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart. EMBO J. 2004;23:885-96 pubmed
    ..These studies raise a new paradigm for the etiology of certain human heart diseases of genetic or environmental origin that may be triggered by dysfunction in RNA processing. ..
  46. Wettschureck N, Rutten H, Zywietz A, Gehring D, Wilkie T, Chen J, et al. Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes. Nat Med. 2001;7:1236-40 pubmed
  47. Rentschler S, Harris B, Kuznekoff L, Jain R, Manderfield L, Lu M, et al. Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways. J Clin Invest. 2011;121:525-33 pubmed publisher
    ..Our results also show that ventricular preexcitation can arise from inappropriate patterning of the AV canal-derived myocardium. ..
  48. Smart N, Risebro C, Melville A, Moses K, Schwartz R, Chien K, et al. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007;445:177-82 pubmed
  49. Gutstein D, Morley G, Fishman G. Conditional gene targeting of connexin43: exploring the consequences of gap junction remodeling in the heart. Cell Commun Adhes. 2001;8:345-8 pubmed
    ..These novel genetic murine models of Cx43 loss of function in the adult mouse heart define gap junctional abnormalities as a key molecular feature of the arrhythmogenic substrate and an important factor in heart dysfunction. ..
  50. Srivastava D, Thomas T, Lin Q, Kirby M, Brown D, Olson E. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet. 1997;16:154-60 pubmed
  51. Koushik S, Wang J, Rogers R, Moskophidis D, Lambert N, Creazzo T, et al. Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack of a heartbeat and abnormal myofibrillar organization. FASEB J. 2001;15:1209-11 pubmed
  52. Chen M, Bi L, Wang Z, Zhao F, Gan X, Wang Y. Time-dependent regulation of neuregulin-1?/ErbB/ERK pathways in cardiac differentiation of mouse embryonic stem cells. Mol Cell Biochem. 2013;380:67-72 pubmed publisher
    ..The ERK1/2 pathway may be involved in the early cardiogenesis, but not in the subtype specification of cardiomyocytes. ..
  53. Caglayan E, Stauber B, Collins A, Lyon C, Yin F, Liu J, et al. Differential roles of cardiomyocyte and macrophage peroxisome proliferator-activated receptor gamma in cardiac fibrosis. Diabetes. 2008;57:2470-9 pubmed publisher
    ..These observations have important implications for potential interventions to prevent cardiac fibrosis. ..