共查询到20条相似文献,搜索用时 31 毫秒
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The human ether-a-go-go-related gene (HERG) product forms the pore-forming subunit of the delayed rectifier K(+) channel in the heart. Unlike the cardiac isoform, the erg K(+) channels in native smooth muscle demonstrate gating properties consistent with a role in maintaining resting potential. We have cloned the smooth muscle isoform of HERG, denoted as erg1-sm, from human and rabbit colon. erg1-sm is truncated by 101 amino acids in the C terminus due to a single nucleotide deletion in the 14th exon. Sequence alignment against HERG showed a substitution of alanine for valine in the S4 domain. When expressed in Xenopus oocytes, erg1-sm currents had much faster activation and deactivation kinetics compared with HERG. Step depolarization positive to -20 mV consistently produced a transient outward component. The threshold for activation of erg1-sm was -60 mV and steady-state conductance was approximately 10-fold greater than HERG near the resting potential of smooth muscle. Site-directed mutagenesis of alanine to valine in the S4 region of erg1-sm converted many of the properties to that of the cardiac HERG, including shifts in the voltage dependence of activation and slowing of deactivation. These studies define the functional role of a novel isoform of the ether-a-go-go-related gene K(+) channel in smooth muscle. 相似文献
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Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. 总被引:40,自引:0,他引:40
D Wang P S Chang Z Wang L Sutherland J A Richardson E Small P A Krieg E N Olson 《Cell》2001,105(7):851-862
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Dominant Negative Murine Serum Response Factor: Alternative Splicing within the Activation Domain Inhibits Transactivation of Serum Response Factor Binding Targets
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Narasimhaswamy S. Belaguli Wei Zhou Thuy-Hanh T. Trinh Mark W. Majesky Robert J. Schwartz 《Molecular and cellular biology》1999,19(7):4582-4591
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Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts 总被引:1,自引:0,他引:1
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Myocardin, a serum response factor (SRF)-dependent cofactor, is a potent activator of smooth muscle gene activity but a poor activator of cardiogenic genes in pluripotent 10T1/2 fibroblasts. Posttranslational modification of GATA4, another myocardin cofactor, by sumoylation strongly activated cardiogenic gene activity. Here, we found that myocardin's activity was strongly enhanced by SUMO-1 via modification of a lysine residue primarily located at position 445 and that the conversion of this residue to arginine (K445R) impaired myocardin transactivation. PIAS1 was involved in governing myocardin activity via its E3 ligase activity that stimulated myocardin sumoylation on an atypical sumoylation site(s) and by its physical association with myocardin. Myocardin initiated the expression of cardiac muscle-specified genes, such as those encoding cardiac alpha-actin and alpha-myosin heavy chain, in an SRF-dependent manner in 10T1/2 fibroblasts, but only in the presence of coexpressed SUMO-1/PIAS1. Thus, SUMO modification acted as a molecular switch to promote myocardin's role in cardiogenic gene expression. 相似文献
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Herrmann J Haas U Gressner AM Weiskirchen R 《Biochimica et biophysica acta》2007,1772(11-12):1250-1257
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《生物化学与生物物理学报:疾病的分子基础》2007,1772(11-12):1250-1257
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Characterization and differential expression of human vascular smooth muscle myosin light chain 2 isoform in nonmuscle cells 总被引:6,自引:0,他引:6
The 20-kDa regulatory myosin light chain (MLC), also known as MLC-2, plays an important role in the regulation of both smooth muscle and nonmuscle cell contractile activity. Phosphorylation of MLC-2 by the enzyme MLC kinase increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity. We have isolated and characterized an MLC-2 cDNA corresponding to the human vascular smooth muscle MLC-2 isoform from a cDNA library derived from umbilical artery RNA. The translation of the in vitro synthesized mRNA, corresponding to the cDNA insert, in a rabbit reticulocyte lysate results in the synthesis of a 20,000-dalton protein that is immunoreactive with antibodies raised against purified chicken gizzard MLC-2. The derived amino acid sequence of the putative human smooth muscle MLC-2 shows only three amino acid differences when compared to chicken gizzard MLC-2. However, comparison with the human cardiac isoform reveals only 48% homology. Blot hybridizations and S1 nuclease analysis indicate that the human smooth muscle MLC-2 isoform is expressed restrictively in smooth muscle tissues such as colon and uterus and in some, but not all, nonmuscle cell lines. Previously reported MLC-2 cDNA from rat aortic smooth muscle cells in culture is ubiquitously expressed in all muscle and nonmuscle cells, and it was suggested that both smooth muscle and nonmuscle MLC-2 proteins are identical and are probably encoded by the same gene. In contrast, the human smooth muscle MLC-2 cDNA that we have characterized from an intact smooth muscle tissue is not expressed in skeletal and cardiac muscles and also in a number of nonmuscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Conditional mutagenesis of the murine serum response factor gene blocks cardiogenesis and the transcription of downstream gene targets 总被引:7,自引:0,他引:7
Niu Z Yu W Zhang SX Barron M Belaguli NS Schneider MD Parmacek M Nordheim A Schwartz RJ 《The Journal of biological chemistry》2005,280(37):32531-32538