Molecular and Cellular Biochemistry

, Volume 184, Issue 1–2, pp 153–167

Molecular characterization of the creatine kinases: and some historical perspectives

  • Wenning Qin
  • Zaza Khuchua
  • Judy Cheng
  • Jaime Boero
  • R. Mark Payne
  • Arnold W. Strauss


Over the last 15 years, molecular characterization of the creatine kinase (CK) gene family has paralleled the molecular revolution of understanding gene structure, function, and regulation. In this review, we present a summary of advances in molecular analysis of the CK gene family with a few vignettes of historical interest. We describe how the muscle CK gene provided an essential model system to examine myogenic regulatory mechanisms, leading to the discovery of the binding site for the MyoD family of basic helix-loop-helix transcription factors essential in skeletal myogenesis and the characterization of the MEF2 family of factors with an A/T rich consensus binding site essential in skeletal myogenesis and cardiogenesis. Cloning and characterization of the four mRNAs and nuclear genes encoding the cytosolic CKs, muscle and brain CKs, and the mitochondrial (Mt) CKs, sarcomeric MtCK and ubiquitous MtCK, has allowed intriguing study of tissue-specific and cell-specific expression of the different CKs and analysis of structural, functional, regulatory, and evolutionary relationships among both the four CK proteins and genes. Current and future studies focus on understanding both cellular energetics facilitated by the CK enzymes, especially energy channelling from the site of production, the mitochondrial matrix and inner membrane, to various cytosolic foci of utilization, and regulation of MtCK gene expression at the cell and tissue-specific level as models of regulation of energy producing genes.

creatine kinase transcription factors myogenesis mitochondrion energy gene family 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Watson JD, Crick FH: Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature 171: 737–738, 1953Google Scholar
  2. 2.
    Nathans D, Smith HO: Restriction endonucleases in the analysis and restructuring of DNA molecules. Annu Rev Biochem 44: 273–293, 1975Google Scholar
  3. 3.
    Lederberg J: Viruses, genes and cells. Bacteriol Rev 21: 133–139, 1957Google Scholar
  4. 4.
    Berg P: The viral genome in transformed cells. Proc R Soc Lond B Biol Sci 177: 65–76, 1971Google Scholar
  5. 5.
    Sharp PA: Splicing of messenger RNA precursors. Science 235: 766–771, 1987Google Scholar
  6. 6.
    Maxam AM, Gilbert W: A new method for sequencing DNA. Proc Natl Acad Sci USA 74: 560–564, 1977Google Scholar
  7. 7.
    Sanger F, Nicklen S, Coulson AR: DNA sequencing with chainterminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977Google Scholar
  8. 8.
    Buskin JN, Hauschka SD: Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. Mol Cell Biol 9: 2627–2640, 1989Google Scholar
  9. 9.
    Gossett LA, Kelvin DJ, Sternberg EA, Olson EN: A new myocytespecific enhancer-binding factor that recognizes a conserved element associated with multiple muscle specific genes. Mol Cell Biol 9: 5022–5033, 1989Google Scholar
  10. 10.
    Lassar AB, Buskin JN, Lockshon D, Davis RL, Apone S, Hauschka SD, Weintraub H: MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell 58: 823–831, 1989Google Scholar
  11. 11.
    Fritz-Wolf K, Schnyder T, Wallimann T, Kabsch W: Structure of mitochondrial creatine kinase. Nature 381: 341–345, 1996Google Scholar
  12. 12.
    Saks VA, Khuchua ZA, Vasilyeva EV, Belikova OY, Kuznetsov AV: Metabolic compartmentation and substrate channelling in muscle cells: Role of coupled creatine kinases in vivo regulation of cellular respiration–a synthesis. Mol Cell Biochem 133/134: 155–192, 1994Google Scholar
  13. 13.
    Weintraub H, Robert D, Tapscott S, Thayer M, Krause M, Benezra R, Blackwell TK, Turner D, Rupp R, Hollenberg S, Zhuang Y, Lassar A: The myoD gene family: Nodal point during specification of the muscle cell lineage. Science 251: 761–766, 1991Google Scholar
  14. 14.
    Olson EN, Perry WM, Schulz RA: Regulation of muscle differentiation by the MEF2 family of MADS box transcription factors. Dev Biol 172: 2–14, 1995Google Scholar
  15. 15.
    Muhlebach SM, Gross M, Wirz T, Walliman T, Perriard JC, Wyss M: Sequence homology and structure predictions of the creatine kinase isoenzymes. Mol Cell Biochem 133/134: 245–262, 1994Google Scholar
  16. 16.
    Schweinfest CW, Kwiatkowski RW, Dottin R: Molecular cloning of a DNA sequence complementary to creatine kinase M mRNA from chickens. Proc Natl Acad Sci USA 79: 4997–5000, 1982Google Scholar
  17. 17.
    Rosenberg UB, Kunz G, Frischauf A, Lehrach H, Mahr R, Eppenberger HM, Perriard JC: Molecular cloning and expression during myogenesis of sequences coding for M-creatine kinase. Proc Natl Acad Sci USA 79: 6589–6592, 1982Google Scholar
  18. 18.
    Ordahl RP, Evans GL, Cooper TA, Kunz G, Perriard J: Complete cDNAderived amino acid sequence of chick muscle creatine kinase. J Biol Chem 259: 15224–15227, 1984Google Scholar
  19. 19.
    Giraudat J, Devillers-Thiery A, Perriard J-C, and Changeux J-P: Complete nucleotide sequence of Torpedo marmorate mRNA coding for the 43,000-dalton v2 protein: Muscle-specific creatine kinase. Proc Natl Acad Sci USA 81: 7313–7317, 1984Google Scholar
  20. 20.
    West BL, Babbitt PC, Mendez B, Baxter JD: Creatine kinase protein sequence encoded by a cDNA made from Torpedo californica electric organ mRNA. Proc Natl Acad Sci USA 81: 7007–7011, 1984Google Scholar
  21. 21.
    Putney S, Herlihy W, Royal N, Pang H, Aposhian HV, Pickering L, Belagaje R, Biemann K, Page D, Kuby S, Schimmel P: Rabbit muscle creatine kinase phosphokinase cDNA cloning, primary structure, and detection of human homologues. J Biol Chem 2591: 4317–14320, 1984Google Scholar
  22. 22.
    Benfield PA, Zivin RA, Miller LS, Sowder R, Smythers GW, Henderson L, Oroszlan S, Pearson ML: Isolation and sequence analysis of cDNA clones coding for rat skeletal muscle creatine kinase. J Biol Chem 259: 14979–14984, 1984Google Scholar
  23. 23.
    Kwiatkowski RW, Schweinfest CW, Dottin RP: Molecular cloning and the complete nucleotide sequence of the creatine kinase-M cDNA from chicken. Nucleic Acids Res 126: 6925–6934, 1984Google Scholar
  24. 24.
    Buskin JN, Jaynes JB, Chamberlain JS, Hauschka SD: The mouse muscle creatine kinase cDNA and deduced amino acid sequences: Comparison to evolutionarily related enzymes. J Mol Evol 22: 334–341, 1985Google Scholar
  25. 25.
    Roman D, Billadello J, Gordon J, Grace A, Sobel B, Strauss A: Complete nucleotide sequence of dog heart creatine kinase mRNA: Conservation of amino acid sequence within and among species. Proc Natl Acad Sci USA 82: 8394–8398, 1985Google Scholar
  26. 26.
    Perryman MB, Kerner SA, Bohlmeyer TJ, Roberts R: Isolation and sequence analysis of a full-length cDNA for human M-creatine kinase. Biochem Biophys Res Comm 140: 981–989, 1986Google Scholar
  27. 27.
    Nigro JM, Schweinfest CW, Rajkovic A, Pavlovic J, Jamal S, Dottin RP, Hart JT, Kamarck ME, Rae PMM, Carty MD, Martin-Deleon P: cDNA cloning and mapping of the human creatine kinase M gene to l9q13. Am J Hum Genet 40: 115–125, 1987Google Scholar
  28. 28.
    Payne RM, Haas RC, Strauss AW: Structural characterization and tissue-specific expression of the mRNAs encoding isoenzymes from two rat mitochondrial creatine kinase genes. Biochim Biophys Acta 1089: 352–361, 1991Google Scholar
  29. 29.
    Trask RV, Strauss AW, Billadello JJ: Developmental regulation and tissue-specific expression of the human muscle creatine kinase gene. J Biol Chem 263: 17142–17149, 1988Google Scholar
  30. 30.
    Klein SC, Haas RC, Perryman B, Billadello JJ, Strauss AW: Regulatory element analysis and structural characterization of the human sarcomeric mitochondrial creatine kinase gene. J Biol Chem 266: 18058–18065, 1991Google Scholar
  31. 31.
    Jaynes JB, Chamberlain JS, Buskin JN, Johnson JE, Hauschka SD: Transcriptional regulation of the muscle creatine kinase gene and regulated expression in transfected mouse myoblasts. Mol Cell Biol 6: 2855–2864, 1986Google Scholar
  32. 32.
    Davis RL, Weintraub H, Lassar AB: Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51: 987–1000, 1987Google Scholar
  33. 33.
    Jaynes JB, Johnson JE, Buskin JN, Gartside CL, Hauschka SD: The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer. Mol Cell Biol 8: 62–70, 1988Google Scholar
  34. 34.
    Johnson JE, Wold BJ, Hauschka SD: Muscle creatine kinase sequence elements regulating skeletal and cardiac muscle expression in transgenic mice. Mol Cell Biol 9: 3393–3399, 1989Google Scholar
  35. 35.
    Edmondson DG, Olson EN: A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev 3: 628–640, 1989Google Scholar
  36. 36.
    Wright WE, Sassoon DA, Lin VK: Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell 56: 607–617, 1989Google Scholar
  37. 37.
    Braun T, Buschhausen-Denker G, Bober E, Tannich E, Arnold HH: A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J 8: 701–709, 1989Google Scholar
  38. 38.
    Rhodes SJ, Konieczny SF: Identification of MRF4: A new member of the muscle regulatory factor gene family. Genes Dev 3: 2050–2061, 1989Google Scholar
  39. 39.
    Braun T, Bober E, Winter B, Rosenthal N, Arnold HH: Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12. EMBO J. 9: 821–831, 1990Google Scholar
  40. 40.
    Miner JH, Wold B: Herculin, a fourth member of the MyoD family of myogenic regulatory genes. Proc Natl Acad Sci USA 87: 1089–1093, 1990Google Scholar
  41. 41.
    Sternberg EA, Spizz G, Perry WM, Vizard D, Weil T, Olson EN: Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene. Mol Cell Biol 8: 2896–2909, 1988Google Scholar
  42. 42.
    Pollock R, Treisman R: Human SRF-related proteins: DNAbinding properties and potential regulatory targets. Genes Dev 5: 2327–2341, 1991Google Scholar
  43. 43.
    Yu YT, Breitbart RE, Smoot LB, Lee Y, Mahdavi V, Nadal-Ginard B: Human myocyte-specific enhancer factor 2 comprises a group of tissuerestricted MADS box transcription factors. Genes Dev 6: 1783–1798, 1992Google Scholar
  44. 44.
    MoIkentin JD, Black BL, Martin JF, Olson EN: Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell 83: 1125–1136, 1995Google Scholar
  45. 45.
    Treisman R: The SRE: A growth factor responsive transcriptional regulator. Sem Cancer Biol 1: 47–58, 1990Google Scholar
  46. 46.
    Minty A, Kedes L: Upstream regions of the human cardiac actin gene that modulate its transcription in muscle cells: Presence of an evolutionarily conserved repeated motif. Mol Cell Biol 6: 2125–2136, 1986Google Scholar
  47. 47.
    Schwarz-Sommer Z, Huijser P, Nacken W, Saedler H, Sommer H: Genetic control of flower development by homeotic genes in Antirrhinum majus. Science 250: 931–936, 1990Google Scholar
  48. 48.
    Lilly B, Zhao B, Ranganayakulu G, Paterson BM, Schulz RA, Olson EN: Requirement of MADS domain transcription factor D-MEF2 for muscle formation in Drosophila. Science 267: 688–693, 1995Google Scholar
  49. 49.
    Pickering L, Pang H, Biemann K, Munro H, Schimmel P: Two tissuespecific isoenzymes of creatine kinase have closely matched amino acid sequences. Proc Natl Acad Sci USA 82: 2310–2314, 1985Google Scholar
  50. 50.
    Benfield PA, Henderson L, Pearson ML: Expression of a rat brain creatine kinase β-galactosidase fusion protein in Escherichia coli and derivation of the complete amino acid sequence of rat brain creatine kinase. Gene 39: 263–267, 1985Google Scholar
  51. 51.
    Kwiatkowski RW, Ehrismann R, Schweinfest CW, Dottin RP: Accumulation of creatine kinase mRNA during myogenesis: Molecular cloning of a B-creatine kinase cDNA. Dev Biol 112: 84–88, 1985Google Scholar
  52. 52.
    Mariman ECM, Broers CAM, Claesen CAA, Tesser GI, Wieringa B: Structure and expression of the human creatine kinase B gene. Genomics 1: 126–137, 1987Google Scholar
  53. 53.
    Kaye FJ, McBride OW, Battey JF, Gazdar AF, Sausville EA: Human creatine kinase-B complementary DNA: Nucleotide sequence, gene expression in lung cancer, and chromosomal assignment to two distinct loci. J Clin Invest 79: 1412–1420, 1987Google Scholar
  54. 54.
    Harford JB, Klausner RD: Coordinate post-transcriptional regulation of ferritin and transferrin receptor expression: The role of regulated RNA-protein interaction. Enzyme 44: 2841, 1990Google Scholar
  55. 55.
    Haas RC, Strauss AW: Separate nuclear genes encode sarcomerespecific and ubiquitous human mitochondrial creatine kinase isoenzymes. J Biol Chem 265: 6921–6927, 1990Google Scholar
  56. 56.
    Villarreal-Levy G, Ma TS, Kerner SA, Roberts R, Perryman MB: Human creatine kinase: Isolation and sequence analysis of cDNA clones for the B subunit, development of subunit specific probes and determination of gene copy number. Biochem Biophys Res Comm 144: 1116–1127, 1987Google Scholar
  57. 57.
    Chern CJ, Tan P, Park H: Chromosomal mapping of human creatine kinase (brain type) using human-rodent somatic cell hybrids. Cytogenet Cell Genet 27: 232–237, 1980Google Scholar
  58. 58.
    Mariman ECM, Schepens JTG, Wieringa B: Complete nucleotide sequence of the human creatine kinase B gene. Nucleic Acid Res 17: 6385, 1989Google Scholar
  59. 59.
    Daouk GH, Kaddurah R, Putney S, Kingston R, Schimmel P: Isolation of a functional human gene for brain creatine kinase. J Biol Chem 263: 2442–2446, 1988Google Scholar
  60. 60.
    Mariman E, Wieringa B: Expression of the gene encoding human brain creatine kinase depends on sequences immediately following the transcription start point. Gene 102: 205–212, 1991Google Scholar
  61. 61.
    Hobson GM, Mitchell MT, Molloy GR, Pearson ML, Benfield PA: Identification of a novel TA-rich DNA binding protein that recognizes a TATA sequence within the brain creatine kinase promoter. Nuclei Acids Res 16: 8925–8944, 1988Google Scholar
  62. 62.
    Hobson G, Molloy GR, Benfield PA: Identification of cis-acting regulatory elements in the promoter region of the rat brain creatine kinase gene. Mol Cell Biol 10: 6533–6543, 1990Google Scholar
  63. 63.
    Gazdar AF, Zweig MH, Carney DN, Van Steirteghen AC, Baylin SB, Minna JD: Levels of creatine kinase and its BB isoenzyme in lung cancer specimens and cultures. Cancer Res 41: 2773–2777, 1981Google Scholar
  64. 64.
    Ritchie ME, Trask RV, Fontanet HL, Billadello JJ: Multiple positive and negative elements regulate human brain creatine kinase gene expression. Nucleic Acids Res 19: 6231–6240, 1991Google Scholar
  65. 65.
    Kuzhikandathil EV, Molloy GR: Transcription of the brain creatine kinase gene in glial cells is modulated by cyclic AMP-dependent protein kinase. J Neurosci Res 39: 7082, 1994Google Scholar
  66. 66.
    Sistermans EA, de Kok YJM, Peters W, Ginsel LA, Jap PHK, Wieringa B: Tissue-and cell-specific distribution of creatine kinase B: A new and highly specific monoclonal antibody for use in immunohistochemistry. Cell Tissue Res 280: 435–446, 1995Google Scholar
  67. 67.
    Leibham D, Wong MW, Cheng TC, Schroeder S, Weil PA, Olson EN, Perry M: Binding of TFIID and MEF2 to the TATA element activates transcription of the Xenopus MyoDa promoter. Mol Cell Biol 14: 686–699, 1994Google Scholar
  68. 68.
    Horlick RA, Hobson GM, Patterson JH, Mitchell MT, Benfield PA: Brain and muscle creatine kinase genes contain common TA-rich recognition protein-binding regulatory elements. Mol Cell Biol 10: 4826–4836, 1990Google Scholar
  69. 69.
    Lyons GE, Muhlebach S, Moser A, Masood R, Paterson BM, Buckingham ME, Perriard J: Developmental regulation of creatine kinase gene expression by myogenic factors in embryonic mouse and chick skeletal muscle. Development 113: 1017–1029, 1991Google Scholar
  70. 70.
    Schulz RA, Chromey C, Lu MF, Zhao B, Olson EN: Expression of the D-MEF2 transcription factor in the Drosophila brain suggests a role in neuronal cell differentiation. Oncogene 12: 1827–1831, 1996Google Scholar
  71. 71.
    Adamson ED: Isoenzyme transition of creatine phosphokinase, aldolase, and phosphoglycerate mutase in differentiating muscle cells. J Embryo Exp Morph 35: 355–367, 1976Google Scholar
  72. 72.
    Ingwall JS: Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res 38: 1115–123, 1976Google Scholar
  73. 73.
    Dym H, Yaffe D: Expression of creatine kinase isoenzymes in myogenic cell lines. Dev Biol 68: 592–599, 1979Google Scholar
  74. 74.
    Trask RV, Billadello JJ: Tissue-specific distribution and developmental regulation of M and B creatine kinase mRNAs. Biochim Biophys Acta 1049: 182–188, 1990Google Scholar
  75. 75.
    Ritchie ME: Characterization of human B creatine kinase gene regulation in the heart in vitro and in vivo. J Biol Chem 271: 25485–25491, 1996Google Scholar
  76. 76.
    Zhao J, Schmieg FI, Simmons DT, Molloy GR: Mouse p53 represses the rat brain creatine kinase gene but activates the rat muscle creatine kinase gene. Mol Cell Biol 14: 8483–8492, 1994Google Scholar
  77. 77.
    Notides A, Gorska J: Estrogen-induced synthesis of a specific protein. Proc Natl Acad Sci USA 56: 230–235, 1966Google Scholar
  78. 78.
    Reiss NA, Kaye AM: Identification of the major component of the estrogen-induced protein of rat uterus as the BB isozyme of CK. J Biol Chem 256: 5741–5749, 1981Google Scholar
  79. 79.
    Somjen D, Weisman Y, Binderman I, Kaye AM: Stimulation of creatine kinase-BB activity by 1 alpha, 25-dihydroxycholecalciferol and 24R, 25-dihydroxycholecalciferol in rat tissues. Biochem J 219: 1037–1041, 1984Google Scholar
  80. 80.
    Somjen D, Kaye AM, Harell A, Weisman Y: Modulation by vitamin D status of the responsiveness of rat bone to gonadal steroids. Endocrinology 125: 1870–1876, 1989Google Scholar
  81. 81.
    Pentecost BT, Mattheiss L, Dickerman HW, Kumar SA: Estrogen regulation of creatine kinase-B in the rat uterus. Mol Endocrinol 4: 1000–1010, 1990Google Scholar
  82. 82.
    Sukovich DA, Mukherjee R, Benfield PA: A novel, cell-type-specific mechanism for estrogen receptor-mediated gene activation in the absence of an estrogen-responsive element. Mol Cell Biol 14: 7134–7143, 1994Google Scholar
  83. 83.
    Jacobs H, Heldt HW, Klingenberg M: High activity of creatine kinase in mitochondrial from muscle and brain and evidence for a separate mitochondrial isoenzyme of creatine kinase. Biochem Biophys Res Commun 16: 516–521, 1964Google Scholar
  84. 84.
    Hossle JP, Schlegel J, Wegmann G, Wyss M, Bohlen P, Eppenberger HM, Wallimann T, Perriard J: Distinct tissue specific mitochondrial creatine kinases from chicken brain and striated muscle with a conserved CK framework. Biochem Biophys Res Commun 151: 408–416, 1988Google Scholar
  85. 85.
    Schlegel J, Wyss M, Schurch U, Schnyder T, Quest A, Wegmann G, Eppenberger HM, Wallimann T: Mitochondrial creatine kinase from cardiac muscle and brain are two distinct isoenzymes but both form octameric molecules. J Biol Chem 263: 16963–16969, 1988Google Scholar
  86. 86.
    Haas RC, Korenfeld C, Zhang Z, Perryman B, Roman D, Strauss AW: Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase. J Biol Chem 264: 2890–2897, 1989Google Scholar
  87. 87.
    Muhlebach SM, Wirz T, Brandle U, Perriard JC: Evolution of the creatine kinases: The chicken acidic type mitochondrial creatine kinase gene as the first nonmammalian gene. J Biol Chem 271: 11920–11929, 1996Google Scholar
  88. 88.
    Kaldis P, Stolz M, Wyss M, Zanolla E, Rothen-Rutishauser B, Vorherr T, Wallimann T: Identification of two distinctly localized mitochondrial creatine kinase isoenzymes in spermatozoa. J Cell Sci 109: 2079–2088, 1996Google Scholar
  89. 89.
    Steeghs K, Peters W, Bruckwilder M, Croes H, van Alewiljk D, Wieringa B: Mouse ubiquitous mitochondrial creatine kinase: Gene organization and consequences from inactivation in mouse embryonic stem cells. DNA Cell Biol 14: 539–553, 1995Google Scholar
  90. 90.
    Stallings RL, Olson EN, Strauss AW, Thompson LH, Bachinski LL, Siciliano MJ: Human creatine kinase genes on chromosome 15 and 19, and proximity of the gene for the muscle form to the genes of apolipoprotein C2 and excision repair. Am J Hum Genet 43: 144–151, 1988Google Scholar
  91. 91.
    Payne RM, Friedman DL, Grant JW, Perryman MB, Strauss AW: Creatine kinase isoenzymes are highly regulated during pregnancy in rat uterus and placenta. Am J Physiol 265: E624–E635, 1993Google Scholar
  92. 92.
    Payne RM, Strauss AW: Developmental expression of sarcomeric and ubiquitous mitochondrial creatine kinase is tissue-specific. Biochim Biophys Acta 1219: 33–38, 1994Google Scholar
  93. 93.
    Friedman DL, Perryman MB: Compartmentation of multiple forms of creatine kinase in the distal nephron of the rat kidney. J Biol Chem 266(33): 22404–22410, 1991Google Scholar
  94. 94.
    Billadello JJ, Kelly DP, Roman DG, Strauss AW: The complete nucleotide sequence of canine brain creatine kinase mRNA: Homology in the coding and 3′ noncoding regions among species. Biochem Biophys Res Commun 138: 392–398, 1986Google Scholar
  95. 95.
    Papenbrock T, Wille W: The 3′ non-coding region of the mouse brain B creatine kinase mRNA: A sequence with exceptional homology among species. Nucleic Acids Res 14: 8690, 1985Google Scholar
  96. 96.
    Konieczny SF, Emerson CP Jr: Complex region of the muscle-specific contractile protein (troponin I) gene. Mol Cell Biol 7: 3065–3075, 1987Google Scholar
  97. 97.
    Smith DJ, Maggio ET, Kenyon GL: Simple alkanethiol groups for temporary blocking of sulfhydryl groups of enzymes. Biochemistry 14: 766–771, 1975Google Scholar
  98. 98.
    Li K, Warner CK, Hodge JA, Minoshima S, Kudoh J, Fukuyama R, Maekawa M, Shimizu Y, Shimizu N, Wallace DC: A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed. J Biol Chem 264(24): 13998–14004, 1989Google Scholar
  99. 99.
    Lenka N, Basu A, Mullick J, Avadhani NG: The role of an E box binding basic helix loop helix protein in the cardiac muscle-specific expression of the rat cytochrome oxidase subunit VIII gene. J Biol Chem 271(47): 30281–30289, 1996Google Scholar
  100. 100.
    Weller PA, Price M, Isenberg H, Edwards YH, Jeffreys AJ: Myoglobin expression: Early induction and subsequent modulation of myoglobin and myoglobin mRNA during myogenesis. Mol Cell Biol 6: 4539–4547, 1986Google Scholar
  101. 101.
    Rossant J: Mouse mutants and cardiac development. New molecular insights into cardiogenesis. Circ Res 78: 349–353, 1996Google Scholar
  102. 102.
    Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP: Nkx-2.5: A novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development 119: 419–431, 1993Google Scholar
  103. 103.
    Komuro I, Izumo S: Csx: A murine homeobox-containing gene specifically expressed in the developing heart. Proc Natl Acad Sci USA 90: 8145–8149, 1993Google Scholar
  104. 104.
    Cross JC, Flannery ML, Blanar MA, Steingrimsson E, Jenkins NA, Copeland NG, Rutter WJ, Werb Z: Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development. Development 121: 2513–2523, 1995Google Scholar
  105. 105.
    Cserjesi P, Brown D, Lyons GE, Olson EN: Expression of the novel basic helixloop-helix gene eHAND in neural crest derivatives and extraembryonic membranes during mouse development. Dev Biol 170: 664–678, 1995Google Scholar
  106. 106.
    Hollenberg SM, Sternglanz R, Cheng PF, Weintraub H: Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system. Mol Cell Biol 15: 3813–3822, 1995Google Scholar
  107. 107.
    Srivastava D, Cserjesi P, Olson EN: A subclass of bHLH proteins required for cardiac morphogenesis. Science 270: 1995–1999, 1995Google Scholar
  108. 108.
    Arceci RJ, King AAJ, Simon MC, Orkin SH, Wilson DB: Mouse GATA-4: A retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol 13: 2235–2246, 1993Google Scholar
  109. 109.
    Tamura S, Wang XH, Maeda M, Futai M: Gastric DNA-binding proteins recognize upstream sequence motifs of parietal cell-specific genes. Proc Natl Acad Sci USA 90: 10876–10880, 1993Google Scholar
  110. 110.
    Kelley C, Blumberg H, Zon LI, Evans T: GATA-4 is a novel transcription factor expressed in endocardium of the developing heart. Development 118: 817–827, 1993Google Scholar
  111. 111.
    Wu X, Golden K, Bodmer R: Heart development in Drosophila requires the segment polarity gene wingless. Dev Biol 169: 619–628, 1995Google Scholar
  112. 112.
    Ranganayakulu G, Schulz RA, Olson EN: Wingless signaling induces nautilus expression in the ventral mesoderm of the Drosophila embryo. Dev Biol 176: 143–148, 1996Google Scholar
  113. 113.
    Bodmer R: The gene tinman is required for specification of the heart and visceral muscles in Drosophila. Development 118: 719–729, 1993Google Scholar
  114. 114.
    Azpiazu N, Frasch M: Tinman and Bagpipe: Two homeobox genes that determine cell fates in the dorsal mesoderm of Drosophila. Genes Dev 7: 1325–1340, 1993Google Scholar
  115. 115.
    Lyons I, Parsons LM, Hartley L, Li R, Andrews TE, Robb L, Harvey RP: Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2–5. Genes Dev 9: 1654–1666, 1995Google Scholar
  116. 116.
    Bessman SP, Carpenter CL: The creatine-creatine phosphate energy shuttle. Annu Rev Biochem 54: 831–862, 1985Google Scholar
  117. 117.
    Rossi AM, Eppenberger HM, Volpe P, Cotrufo R, Wallimann T: Muscletype MM creatine kinase is specifically bound to sarcoplasmic reticulum and can transport Ca2+ uptake and regulate local ATP/ADP ratios. J Biol Chem 265: 5258–5266, 1990Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Wenning Qin
    • 1
  • Zaza Khuchua
    • 1
  • Judy Cheng
    • 1
  • Jaime Boero
    • 1
  • R. Mark Payne
    • 1
  • Arnold W. Strauss
    • 1
  1. 1.Departments of Pediatrics and Molecular Biology and PharmacologyWashington University School of Medicine and St. Louis Children's HospitalSt. LouisUSA

Personalised recommendations