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Intracellular calcium and myosin isoform ... IIa myosin heavy chain promoter
Intracellular calcium and myosin isoform transitions. Calcineurin and calcium-calmodulin kinase pathways regulate preferential activation of the IIa myosin heavy chain promoter.
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Intracellular calcium levels can have profound effects on muscle biology via alterations in gene expression. In particular, intracellular calcium levels increase during muscle activation and are thought to underlie fast-to-slow shifts in muscle gene expression. In the present work, we determined that increased intracellular calcium has a significant effect on the activity of the adult fast myosin heavy chain (MyHC) promoters in the order of MyHC IIa>> IId/x > IIb. We have identified the pathways by which the calcium signal mediates increased activation of the MyHC IIa promoter. Inhibition of calcineurin or calcium-calmodulin kinase greatly attenuates ionophore-induced activation of the MyHC IIa promoter, whereas protein kinase C inhibitors have no effect. Inhibition and overexpression studies with members of the mitogen-activated protein kinase family reveal roles for MEK1/MEK2 and MEKK1, but not p38 or phosphatidylinositol 3-kinase. Downstream mediators of these effects are the activities of the MEF-2 and NFAT transcription factors, whose binding sites in the MyHC IIa promoter are required for calcium-induced activation of the MyHC IIa promoter.
Allen DL, Leinwand LA
The Journal of biological chemistry
2002-11-22 00:00
277
47
45323-30
Animals,Binding Sites,Ca(2+)-Calmodulin Dependent Protein Kinase,Calcimycin,Calcineurin,Calcium,Calcium Signaling,Cell Line,DNA-Binding Proteins,Enzyme Inhibitors,Genes, Reporter,Humans,Ionophores,MAP Kinase Signaling System,Mice,Mitogen-Activated Protein Kinases,Muscle, Skeletal,Mutagenesis, Site-Directed,Myosin Heavy Chains,NFATC Transcription Factors,Nuclear Proteins,Promoter Regions (Genetics),Protein Isoforms,Protein Kinase C,Transcription Factors,DNA-Binding Proteins,ELF4 protein, human,Elf4 protein, mouse,Enzyme Inhibitors,Ionophores,Myosin Heavy Chains,NFATC Transcription Factors,Nuclear Proteins,Protein Isoforms,Transcription Factors,Calcimycin,Calcium,Ca(2+)-Calmodulin Dependent Protein Kinase,Mitogen-Activated Protein Kinases,Protein Kinase C,Calcineurin
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA allendlstripecoloradoedu
J. Biol. Chem.
NIGMS R01-GM29090
0021-9258
10.1074/jbc.M208302200
M208302200
737
True
12235157
