请输入您要查询的百科知识：

　

词条 MYL2
释义

  1. Structure

  2. Function

  3. Expression patterns during cardiac development

  4. Phosphorylation sites and regulators

  5. Clinical significance

      Effects on cardiac muscle contraction    Effects on adult cardiac torsion, function and disease  

  6. Animal studies

  7. Notes

  8. References

  9. Further reading

{{Infobox_gene}}Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the MYL2 gene.[1][2] This cardiac ventricular RLC isoform is distinct from that expressed in skeletal muscle (MYLPF), smooth muscle (MYL12B) and cardiac atrial muscle (MYL7).[3]

Ventricular myosin light chain-2 (MLC-2v) refers to the ventricular cardiac muscle form of myosin light chain 2 (Myl2). MLC-2v is a 19-KDa protein composed of 166 amino acids, that belongs to the EF-hand Ca2+ binding superfamily.[4] MLC-2v interacts with the neck/tail region of the muscle thick filament protein myosin to regulate myosin motility and function.[5]

Structure

Cardiac, ventricular RLC is an 18.8 kDa protein composed of 166 amino acids.[6][7] RLC and the second ventricular light chain, essential light chain (ELC, MYL3), are non-covalently bound to IQXXXRGXXXR motifs in the 9 nm S1-S2 lever arm of the myosin head,[8] both alpha (MYH6) and beta (MYH7) isoforms. Both light chains are members of the EF-hand superfamily of proteins, which possess two helix-loop-helix motifs in two globular domains connected by an alpha-helical linker.

Function

The N-terminal EF-hand domain of RLC binds calcium/magnesium at activating concentrations,[9] however the dissociation rate is too slow to modulate cardiac contractility on a beat-by-beat basis.[10] Perturbing the calcium binding region of RLC through site-directed mutagenesis (D47A) decreased tension and stiffness in isolated, skinned skeletal muscle fibers,[11] suggesting that the conformational change induced by calcium binding to RLC is functionally important.[12]

Another mode of RLC modulation lies in its ability to be modified by phosphorylation and deamidation in the N-terminal region, resulting in significant charge alterations of the protein. RLC is phosphorylated by a cardiac-specific myosin light chain kinase (MYLK3), which was recently cloned.[13] Studies have supported a role for myosin phosphatase targeting subunit 2 (MYPT2,PPP1R12B) in the dephosphorylation of RLC.[14] Human RLC has an Asparagine at position 14 (Threonine in mouse) and a Serine at position 15 (same in mouse). Endogenous RLC exists as a mixture of unmodified (typically ~50%), singly-modified (either N14 deamidation or S15 phosphorylation) and doubly modified (N14 deamidation and S15 phosphorylation) protein.[3] Both deamidation and phosphorylation contribute negative charge to the N-terminal region of RLC, undoubtedly altering its interaction with the C-terminal myosin alpha helical domain. Functional studies have supported a role for RLC phosphorylation in modulating cardiac myosin crossbridge kinetics. It is well established that RLC phosphorylation enhances myofilament sensitivity to calcium in isometrically-contracting, skinned cardiac fibers.[15][16] It was also demonstrated that a lack of RLC phosphorylation decreases tension cost (isometric force/ATPase rate at a given pCa), suggesting that RLC phosphorylation augments cycling kinetics of myosin.[17] It has been proposed that RLC phosphorylation promotes a "swing-out" of myosin heads, facilitating weak-to-strong crossbridge binding to actin per unit calcium.[18] Additional insights regarding RLC phosphorylation in beating hearts have come from in vivo studies. Adult mice expressing a non-phosphorylatable cardiac RLC (TG-RLC(P-)) exhibited significant decreases in load-dependent[19] and load-independent measures of contractility.[17] In TG-RLC(P-), the time for the heart to reach peak elastance during ejection was elongated, ejection capacity was decreased and the inotropic response to dobutamine was blunted.[17] It is also clear that ablation of RLC phosphorylation in vivo induces alterations in the phosphorylation of other sarcomeric proteins, namely cardiac myosin binding protein C and cardiac troponin I. Moreover, RLC phosphorylation, specifically, appears to be necessary for a normal inotropic response to dobutamine.[17] In agreement with these findings, a second in vivo model, cardiac myosin light chain kinase (MYLK3) knockout (cMLCK neo/neo), showed depressed fractional shortening, progressing to left ventricular hypertrophy by 4–5 months of age.[20] Taken together, these studies clearly demonstrate that RLC phosphorylation regulates cardiac dynamics in beating hearts, and is critical for eliciting a normal sympathetic response.

Expression patterns during cardiac development

MLC-2v plays an essential role in early embryonic cardiac development and function.[21] and represents one of the earliest markers of ventricular specification.[22] During early development (E7.5-8.0), MLC-2v is expressed within the cardiac crescent. The expression pattern of MLC-2v becomes restricted to the ventricular segment of the linear heart tube at E8.0 and remains restricted within the ventricle into adulthood.[22][23]

Phosphorylation sites and regulators

Recent studies have highlighted a critical role for MLC2v phosphorylation in cardiac torsion, function and disease.[29] In cardiac muscle, the critical phosphorylation sites have been identified as Ser14/Ser15 in the mouse heart and Ser15 in the human heart.[24] The major kinase responsible for MLC-2v phosphorylation has been identified as cardiac myosin light chain kinase (MLCK), encoded for by Mylk3.[24][25] Loss of cardiac MLCK in mice results in loss of cardiac MLC-2v phosphorylation and cardiac abnormalities.[20][26]

Clinical significance

Mutations in MYL2 have been associated with familial hypertrophic cardiomyopathy (FHC). Ten FHC mutations have been identified in RLC: E22K, A13T, N47K, P95A, F18L, R58Q, IVS6-1G>C, L103E, IVS5-2A>G, D166V. The first three-E22K, A13T and N47K-have been associated with an unusual mid-ventricular chamber obstruction type of hypertrophy.[27][28] Three mutations-R58Q, D166V and IVS5-2-are associated with more malignant outcomes, manifesting with sudden cardiac death or at earlier ages.[29][30][31][32] Functional studies demonstrate that FHC mutations in RLC affect its ability to both be phosphorylated and to bind calcium/magnesium.[33]

Effects on cardiac muscle contraction

MLC-2v plays an important role in cross-bridge cycling kinetics and cardiac muscle contraction.[34] MLC-2v phosphorylation at Ser14 and Ser15 increases myosin lever arm stiffness and promotes myosin head diffusion, which altogether slow down myosin kinetics and prolong the duty cycle as a means to fine-tune myofilament Ca2+ sensitivity to force.[34]

Effects on adult cardiac torsion, function and disease

A gradient in the levels of both MLC2v phosphorylation and its kinase, cardiac MLCK, has been shown to exist across the human heart from endocardium (low phosphorylation) to epicardium (high phosphorylation).[35] The existence of this gradient has been proposed to impact cardiac torsion due to the relative spatial orientation of endocardial versus epicardial myofibers.[35] In support of this, recent studies have shown that MLC-2v phosphorylation is critical in regulating left ventricular torsion.[26][34] Variations in myosin cycling kinetics and contractile properties as a result of differential MLC-2v phosphorylation (Ser14/15) influence both epicardial and endocardial myofiber tension development and recovery to control cardiac torsion and myofiber strain mechanics.[26][34]

A number of human studies have implicated loss of MLC-2v phosphorylation in the pathogenesis of human dilated cardiomyopathy and heart failure.[24][36][37][38][39] MLC-2v dephosphorylation has also been reported in human patients carrying a rare form of familial hypertrophic cardiomyopathy (FHC) based on specific MLC-2v and MLCK mutations.[12][35][40]

Animal studies

MLC-2v plays a key role in the regulation of cardiac muscle contraction, through its interactions with myosin.[41] Loss of MLC-2v in mice is associated with ultrastructural defects in sarcomere assembly and results in dilated cardiomyopathy and heart failure with reduced ejection fraction, leading to embryonic lethality at E12.5.[21] More recently, a mutation in zebrafish tell tale heart (telm225) that encodes MLC-2, demonstrated that cardiac MLC-2 is required for thick filament stabilization and contractility in the embryonic zebrafish heart.[42]

The role of Myl2 mutations in pathogenesis has been determined through the generation of a number of mouse models.[34][43][44] Transgenic mice overexpressing the human MLC-2v R58Q mutation, which is associated with FHC has been shown to lead to a reduction in MLC-2v phosphorylation in hearts.[43] These mice exhibited features of FHC, including diastolic dysfunction that progressed with age.[43] Similarly, cardiac overexpression of another FHC-associated MLC-2v mutation (D166V) results in loss of MLC-2v phosphorylation in mouse hearts.[44] In addition to these findings, MLC-2v dephosphorylation in mice results in cardiac dilatation and dysfunction associated with features reminiscent of dilated cardiomyopathy, leading to heart failure and premature death.[14][26][34] Altogether these studies highlight a role for MLC-2v phosphorylation in adult heart function. These studies also suggest that torsion defects might be an early manifestation of dilated cardiomyopathy consequent to loss of MLC-2v phosphorylation.[34] MLC-2v also plays an important role in cardiac stress associated with hypertrophy.[26][34] In a novel MLC2v Ser14Ala/Ser15Ala knockin mouse model, complete loss of MLC2v (Ser14/Ser15) phosphorylation led to a worsened and differential (eccentric as opposed to concentric) response to pressure overload-induced hypertrophy.[34] In addition, mice lacking cardiac MLCK display heart failure and experience premature death in response to both pressure overload and swimming induced hypertrophy.[26] Consistent with these findings, a cardiac-specific transgenic mouse model overexpressing cardiac MLCK attenuated the response to cardiac hypertrophy induced by pressure overload.[26] Furthermore, in a cardiac-specific transgenic mouse model overexpressing skeletal myosin light chain kinase, the response to cardiac hypertrophy induced by treadmill exercise or isoproterenol was also attenuated.[45] These studies further highlight the therapeutic potential of increasing MLC-2v phosphorylation in settings of cardiac pathological stress.

Notes

{{Academic-written review
| wikidate = 2015
| journal = Gene
| title = {{#property:P1476|from=Q35832615}}
| authors = {{#property:P2093|from=Q35832615}}
| date = {{#property:P577|from=Q35832615}}
| volume = {{#property:P478|from=Q35832615}}
| issue = {{#property:P433|from=Q35832615}}
| pages = {{#property:P304|from=Q35832615}}
| doi = {{#property:P356|from=Q35832615}}
| pmid = {{#property:P698|from=Q35832615}}
| pmc = {{#property:P932|from=Q35832615}}
}}

References

1. ^{{cite journal | vauthors = Macera MJ, Szabo P, Wadgaonkar R, Siddiqui MA, Verma RS | title = Localization of the gene coding for ventricular myosin regulatory light chain (MYL2) to human chromosome 12q23-q24.3 | journal = Genomics | volume = 13 | issue = 3 | pages = 829–31 | date = Jul 1992 | pmid = 1386340 | pmc = | doi = 10.1016/0888-7543(92)90161-K }}
2. ^{{cite web | title = Entrez Gene: MYL2 myosin, light chain 2, regulatory, cardiac, slow| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4633| accessdate = }}
3. ^1 {{cite journal | vauthors = Scruggs SB, Solaro RJ | title = The significance of regulatory light chain phosphorylation in cardiac physiology | journal = Archives of Biochemistry and Biophysics | volume = 510 | issue = 2 | pages = 129–34 | date = Jun 2011 | pmid = 21345328 | pmc = 3114105 | doi = 10.1016/j.abb.2011.02.013 }}
4. ^{{cite journal | vauthors = Grabarek Z | title = Structural basis for diversity of the EF-hand calcium-binding proteins | journal = Journal of Molecular Biology | volume = 359 | issue = 3 | pages = 509–25 | date = Jun 2006 | pmid = 16678204 | doi = 10.1016/j.jmb.2006.03.066 }}
5. ^{{cite journal | vauthors = Rayment I, Holden HM, Whittaker M, Yohn CB, Lorenz M, Holmes KC, Milligan RA | title = Structure of the actin-myosin complex and its implications for muscle contraction | journal = Science | volume = 261 | issue = 5117 | pages = 58–65 | date = Jul 1993 | pmid = 8316858 | doi=10.1126/science.8316858}}
6. ^{{cite web | url = http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q6IB42 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = MYL2 protein }}
7. ^{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
8. ^{{cite journal | vauthors = Rayment I, Rypniewski WR, Schmidt-Bäse K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM | title = Three-dimensional structure of myosin subfragment-1: a molecular motor | journal = Science | volume = 261 | issue = 5117 | pages = 50–8 | year = 1993 | pmid = 8316857 | doi = 10.1126/science.8316857| url = }}
9. ^{{cite journal | vauthors = Morimoto K, Harrington WF | title = Evidence for structural changes in vertebrate thick filaments induced by calcium | journal = Journal of Molecular Biology | volume = 88 | issue = 3 | pages = 693–709 | date = Sep 1974 | pmid = 4449125 | doi = 10.1016/0022-2836(74)90417-3}}
10. ^{{cite journal | vauthors = Bagshaw CR | title = On the location of the divalent metal binding sites and the light chain subunits of vertebrate myosin | journal = Biochemistry | volume = 16 | issue = 1 | pages = 59–67 | year = 1977 | pmid = 188447 | doi = 10.1021/bi00620a010| url = }}
11. ^{{cite journal | vauthors = Diffee GM, Patel JR, Reinach FC, Greaser ML, Moss RL | title = Altered kinetics of contraction in skeletal muscle fibers containing a mutant myosin regulatory light chain with reduced divalent cation binding | journal = Biophysical Journal | volume = 71 | issue = 1 | pages = 341–50 | date = Jul 1996 | pmid = 8804617 | pmc = 1233485 | doi = 10.1016/S0006-3495(96)79231-7 }}
12. ^1 {{cite journal | vauthors = Szczesna D, Ghosh D, Li Q, Gomes AV, Guzman G, Arana C, Zhi G, Stull JT, Potter JD | title = Familial hypertrophic cardiomyopathy mutations in the regulatory light chains of myosin affect their structure, Ca2+ binding, and phosphorylation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 10 | pages = 7086–92 | date = Mar 2001 | pmid = 11102452 | doi = 10.1074/jbc.M009823200 }}
13. ^{{cite journal | vauthors = Chan JY, Takeda M, Briggs LE, Graham ML, Lu JT, Horikoshi N, Weinberg EO, Aoki H, Sato N, Chien KR, Kasahara H | title = Identification of cardiac-specific myosin light chain kinase | journal = Circulation Research | volume = 102 | issue = 5 | pages = 571–80 | date = Mar 2008 | pmid = 18202317 | pmc = 2504503 | doi = 10.1161/CIRCRESAHA.107.161687 }}
14. ^1 {{cite journal | vauthors = Mizutani H, Okamoto R, Moriki N, Konishi K, Taniguchi M, Fujita S, Dohi K, Onishi K, Suzuki N, Satoh S, Makino N, Itoh T, Hartshorne DJ, Ito M | title = Overexpression of myosin phosphatase reduces Ca(2+) sensitivity of contraction and impairs cardiac function | journal = Circulation Journal | volume = 74 | issue = 1 | pages = 120–8 | date = Jan 2010 | pmid = 19966500 | doi = 10.1253/circj.cj-09-0462}}
15. ^{{cite journal | vauthors = Morano I, Hofmann F, Zimmer M, Rüegg JC | title = The influence of P-light chain phosphorylation by myosin light chain kinase on the calcium sensitivity of chemically skinned heart fibres | journal = FEBS Letters | volume = 189 | issue = 2 | pages = 221–4 | date = Sep 1985 | pmid = 3840099 | doi = 10.1016/0014-5793(85)81027-9}}
16. ^{{cite journal | vauthors = Olsson MC, Patel JR, Fitzsimons DP, Walker JW, Moss RL | title = Basal myosin light chain phosphorylation is a determinant of Ca2+ sensitivity of force and activation dependence of the kinetics of myocardial force development | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 287 | issue = 6 | pages = H2712–8 | date = Dec 2004 | pmid = 15331360 | doi = 10.1152/ajpheart.01067.2003 }}
17. ^1 2 3 {{cite journal | vauthors = Scruggs SB, Hinken AC, Thawornkaiwong A, Robbins J, Walker LA, de Tombe PP, Geenen DL, Buttrick PM, Solaro RJ | title = Ablation of ventricular myosin regulatory light chain phosphorylation in mice causes cardiac dysfunction in situ and affects neighboring myofilament protein phosphorylation | journal = The Journal of Biological Chemistry | volume = 284 | issue = 8 | pages = 5097–106 | date = Feb 2009 | pmid = 19106098 | pmc = 2643522 | doi = 10.1074/jbc.M807414200 }}
18. ^{{cite journal | vauthors = Metzger JM, Greaser ML, Moss RL | title = Variations in cross-bridge attachment rate and tension with phosphorylation of myosin in mammalian skinned skeletal muscle fibers. Implications for twitch potentiation in intact muscle | journal = The Journal of General Physiology | volume = 93 | issue = 5 | pages = 855–83 | date = May 1989 | pmid = 2661721 | pmc = 2216237 | doi = 10.1085/jgp.93.5.855}}
19. ^{{cite journal | vauthors = Sanbe A, Fewell JG, Gulick J, Osinska H, Lorenz J, Hall DG, Murray LA, Kimball TR, Witt SA, Robbins J | title = Abnormal cardiac structure and function in mice expressing nonphosphorylatable cardiac regulatory myosin light chain 2 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 30 | pages = 21085–94 | date = Jul 1999 | pmid = 10409661 | doi = 10.1074/jbc.274.30.21085}}
20. ^1 {{cite journal | vauthors = Ding P, Huang J, Battiprolu PK, Hill JA, Kamm KE, Stull JT | title = Cardiac myosin light chain kinase is necessary for myosin regulatory light chain phosphorylation and cardiac performance in vivo | journal = The Journal of Biological Chemistry | volume = 285 | issue = 52 | pages = 40819–29 | date = Dec 2010 | pmid = 20943660 | pmc = 3003383 | doi = 10.1074/jbc.M110.160499 }}
21. ^1 {{cite journal | vauthors = Chen J, Kubalak SW, Minamisawa S, Price RL, Becker KD, Hickey R, Ross J, Chien KR | title = Selective requirement of myosin light chain 2v in embryonic heart function | journal = The Journal of Biological Chemistry | volume = 273 | issue = 2 | pages = 1252–6 | date = Jan 1998 | pmid = 9422794 | doi=10.1074/jbc.273.2.1252}}
22. ^1 {{cite journal | vauthors = O'Brien TX, Lee KJ, Chien KR | title = Positional specification of ventricular myosin light chain 2 expression in the primitive murine heart tube | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 11 | pages = 5157–61 | date = Jun 1993 | pmid = 8506363 | doi=10.1073/pnas.90.11.5157 | pmc=46674}}
23. ^{{cite journal | vauthors = Ross RS, Navankasattusas S, Harvey RP, Chien KR | title = An HF-1a/HF-1b/MEF-2 combinatorial element confers cardiac ventricular specificity and established an anterior-posterior gradient of expression | journal = Development | volume = 122 | issue = 6 | pages = 1799–809 | date = Jun 1996 | pmid = 8674419 }}
24. ^1 2 {{cite journal | vauthors = Scruggs SB, Reisdorph R, Armstrong ML, Warren CM, Reisdorph N, Solaro RJ, Buttrick PM | title = A novel, in-solution separation of endogenous cardiac sarcomeric proteins and identification of distinct charged variants of regulatory light chain | journal = Molecular & Cellular Proteomics | volume = 9 | issue = 9 | pages = 1804–18 | date = Sep 2010 | pmid = 20445002 | doi = 10.1074/mcp.M110.000075 | pmc=2938104}}
25. ^{{cite journal | vauthors = Seguchi O, Takashima S, Yamazaki S, Asakura M, Asano Y, Shintani Y, Wakeno M, Minamino T, Kondo H, Furukawa H, Nakamaru K, Naito A, Takahashi T, Ohtsuka T, Kawakami K, Isomura T, Kitamura S, Tomoike H, Mochizuki N, Kitakaze M | title = A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart | journal = The Journal of Clinical Investigation | volume = 117 | issue = 10 | pages = 2812–24 | date = Oct 2007 | pmid = 17885681 | doi = 10.1172/JCI30804 | pmc=1978424}}
26. ^1 2 3 4 5 6 {{cite journal | vauthors = Warren SA, Briggs LE, Zeng H, Chuang J, Chang EI, Terada R, Li M, Swanson MS, Lecker SH, Willis MS, Spinale FG, Maupin-Furlowe J, McMullen JR, Moss RL, Kasahara H | title = Myosin light chain phosphorylation is critical for adaptation to cardiac stress | journal = Circulation | volume = 126 | issue = 22 | pages = 2575–88 | date = Nov 2012 | pmid = 23095280 | doi = 10.1161/CIRCULATIONAHA.112.116202 | pmc=3510779}}
27. ^{{cite journal | vauthors = Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND | title = Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle | journal = Nature Genetics | volume = 13 | issue = 1 | pages = 63–9 | date = May 1996 | pmid = 8673105 | doi = 10.1038/ng0596-63 }}
28. ^{{cite journal | vauthors = Andersen PS, Havndrup O, Bundgaard H, Moolman-Smook JC, Larsen LA, Mogensen J, Brink PA, Børglum AD, Corfield VA, Kjeldsen K, Vuust J, Christiansen M | title = Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations | journal = Journal of Medical Genetics | volume = 38 | issue = 12 | pages = E43 | date = Dec 2001 | pmid = 11748309 | pmc = 1734772 | doi = 10.1136/jmg.38.12.e43}}
29. ^{{cite journal | vauthors = Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M | title = Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy | journal = Circulation | volume = 107 | issue = 17 | pages = 2227–32 | date = May 2003 | pmid = 12707239 | doi = 10.1161/01.CIR.0000066323.15244.54 }}
30. ^{{cite journal | vauthors = Flavigny J, Richard P, Isnard R, Carrier L, Charron P, Bonne G, Forissier JF, Desnos M, Dubourg O, Komajda M, Schwartz K, Hainque B | title = Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy | journal = Journal of Molecular Medicine | volume = 76 | issue = 3–4 | pages = 208–14 | date = Mar 1998 | pmid = 9535554 | doi = 10.1007/s001090050210}}
31. ^{{cite journal | vauthors = Kabaeva ZT, Perrot A, Wolter B, Dietz R, Cardim N, Correia JM, Schulte HD, Aldashev AA, Mirrakhimov MM, Osterziel KJ | title = Systematic analysis of the regulatory and essential myosin light chain genes: genetic variants and mutations in hypertrophic cardiomyopathy | journal = European Journal of Human Genetics | volume = 10 | issue = 11 | pages = 741–8 | date = Nov 2002 | pmid = 12404107 | doi = 10.1038/sj.ejhg.5200872 }}
32. ^{{cite journal | vauthors = Mörner S, Richard P, Kazzam E, Hellman U, Hainque B, Schwartz K, Waldenström A | title = Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden | journal = Journal of Molecular and Cellular Cardiology | volume = 35 | issue = 7 | pages = 841–9 | date = Jul 2003 | pmid = 12818575 | doi = 10.1016/s0022-2828(03)00146-9}}
33. ^{{cite journal | vauthors = Harris SP, Lyons RG, Bezold KL | title = In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament | journal = Circulation Research | volume = 108 | issue = 6 | pages = 751–64 | date = Mar 2011 | pmid = 21415409 | doi = 10.1161/CIRCRESAHA.110.231670 | pmc=3076008}}
34. ^1 2 3 4 5 6 7 8 {{cite journal | vauthors = Sheikh F, Ouyang K, Campbell SG, Lyon RC, Chuang J, Fitzsimons D, Tangney J, Hidalgo CG, Chung CS, Cheng H, Dalton ND, Gu Y, Kasahara H, Ghassemian M, Omens JH, Peterson KL, Granzier HL, Moss RL, McCulloch AD, Chen J | title = Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease | journal = The Journal of Clinical Investigation | volume = 122 | issue = 4 | pages = 1209–21 | date = Apr 2012 | pmid = 22426213 | doi = 10.1172/JCI61134 | pmc=3314469}}
35. ^1 2 {{cite journal | vauthors = Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, Aletras AH, Wen H, Epstein ND | title = The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation | journal = Cell | volume = 107 | issue = 5 | pages = 631–41 | date = Nov 2001 | pmid = 11733062 | doi=10.1016/s0092-8674(01)00586-4}}
36. ^{{cite journal | vauthors = Morano I | title = Effects of different expression and posttranslational modifications of myosin light chains on contractility of skinned human cardiac fibers | journal = Basic Research in Cardiology | volume = 87 Suppl 1 | pages = 129–41 | date = 1992 | pmid = 1386730 | doi=10.1007/978-3-642-72474-9_11}}
37. ^{{cite journal | vauthors = van Der Velden J, Klein LJ, Zaremba R, Boontje NM, Huybregts MA, Stooker W, Eijsman L, de Jong JW, Visser CA, Visser FC, Stienen GJ | title = Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts | journal = Circulation | volume = 104 | issue = 10 | pages = 1140–6 | date = Sep 2001 | pmid = 11535570 | doi=10.1161/hc3501.095485}}
38. ^{{cite journal | vauthors = van der Velden J, Papp Z, Zaremba R, Boontje NM, de Jong JW, Owen VJ, Burton PB, Goldmann P, Jaquet K, Stienen GJ | title = Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins | journal = Cardiovascular Research | volume = 57 | issue = 1 | pages = 37–47 | date = Jan 2003 | pmid = 12504812 | doi=10.1016/s0008-6363(02)00606-5}}
39. ^{{cite journal | vauthors = van der Velden J, Papp Z, Boontje NM, Zaremba R, de Jong JW, Janssen PM, Hasenfuss G, Stienen GJ | title = The effect of myosin light chain 2 dephosphorylation on Ca2+ -sensitivity of force is enhanced in failing human hearts | journal = Cardiovascular Research | volume = 57 | issue = 2 | pages = 505–14 | date = Feb 2003 | pmid = 12566123 | doi=10.1016/s0008-6363(02)00662-4}}
40. ^{{cite journal | vauthors = Jacques AM, Briceno N, Messer AE, Gallon CE, Jalilzadeh S, Garcia E, Kikonda-Kanda G, Goddard J, Harding SE, Watkins H, Esteban MT, Tsang VT, McKenna WJ, Marston SB | title = The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy | journal = Cardiovascular Research | volume = 79 | issue = 3 | pages = 481–91 | date = Aug 2008 | pmid = 18411228 | doi = 10.1093/cvr/cvn094 | pmc=2492731}}
41. ^1 {{cite journal | vauthors = Sheikh F, Lyon RC, Chen J | title = Getting the skinny on thick filament regulation in cardiac muscle biology and disease | journal = Trends in Cardiovascular Medicine | volume = 24 | issue = 4 | pages = 133–41 | date = May 2014 | pmid = 23968570 | doi = 10.1016/j.tcm.2013.07.004 | pmc=3877703}}
42. ^{{cite journal | vauthors = Rottbauer W, Wessels G, Dahme T, Just S, Trano N, Hassel D, Burns CG, Katus HA, Fishman MC | title = Cardiac myosin light chain-2: a novel essential component of thick-myofilament assembly and contractility of the heart | journal = Circulation Research | volume = 99 | issue = 3 | pages = 323–31 | date = Aug 2006 | pmid = 16809551 | doi = 10.1161/01.RES.0000234807.16034.fe }}
43. ^1 2 {{cite journal | vauthors = Abraham TP, Jones M, Kazmierczak K, Liang HY, Pinheiro AC, Wagg CS, Lopaschuk GD, Szczesna-Cordary D | title = Diastolic dysfunction in familial hypertrophic cardiomyopathy transgenic model mice | journal = Cardiovascular Research | volume = 82 | issue = 1 | pages = 84–92 | date = Apr 2009 | pmid = 19150977 | doi = 10.1093/cvr/cvp016 | pmc=2721639}}
44. ^1 {{cite journal | vauthors = Muthu P, Kazmierczak K, Jones M, Szczesna-Cordary D | title = The effect of myosin RLC phosphorylation in normal and cardiomyopathic mouse hearts | journal = Journal of Cellular and Molecular Medicine | volume = 16 | issue = 4 | pages = 911–9 | date = Apr 2012 | pmid = 21696541 | doi = 10.1111/j.1582-4934.2011.01371.x | pmc=3193868}}
45. ^{{cite journal | vauthors = Huang J, Shelton JM, Richardson JA, Kamm KE, Stull JT | title = Myosin regulatory light chain phosphorylation attenuates cardiac hypertrophy | journal = The Journal of Biological Chemistry | volume = 283 | issue = 28 | pages = 19748–56 | date = Jul 2008 | pmid = 18474588 | doi = 10.1074/jbc.M802605200 | pmc=2443673}}

Further reading

{{refbegin|33em}}
  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hyper-card GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview]
  • [https://web.archive.org/web/20110722014038/http://cmkb.cellmigration.org/report.cgi?report=orth_overview&gene_id=4633 MYL2] Info with links in the Cell Migration Gateway
{{refend}}

1 : EF-hand-containing proteins
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/11 8:46:44