Roles of Myosin Light Chain Kinases in the Heart
肌球蛋白轻链激酶在心脏中的作用
基本信息
- 批准号:7564721
- 负责人:
- 金额:$ 38.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-02-01 至 2011-01-31
- 项目状态:已结题
- 来源:
- 关键词:AblationActinsAffectBiochemicalBiosensorBirthBreedingCalciumCalmodulinCardiacCardiac MyocytesCardiac MyosinsCardiomyopathiesCatheterizationCellsCongestive Heart FailureConsensusDataDefectDevelopmentEchocardiographyEmbryonic HeartFiberFluorescence Resonance Energy TransferGenesHeartHeart AtriumHeart HypertrophyHistologyInvestigationKnock-outKnockout MiceLeadLeftLengthLightMeasurementMeasuresMusMuscle CellsMyocardiumMyosin ATPaseMyosin Light Chain KinaseMyosin Light ChainsMyosin Type IINewborn InfantNonmuscle Myosin Type IIBPerformancePhosphorylationPhosphotransferasesPhysiologicalPlayProceduresPropertyProtein IsoformsProteinsRegulationResearchRoleSarcomeresSkeletal Muscle MyosinsSkinStressStructureTestingThick FilamentTissuesTransgenic MiceTransgenic OrganismsTransmission Electron MicroscopyVentricularWeightbasefiber cellgain of functionin vivoindexinginsightknockout animalknockout genenoveloverexpressionresponse
项目摘要
Contraction of heart muscle results from the cyclic interaction of myosin with actin under the regulation of
sarcomeric thin and thick filament proteins. Based on results from skinned fibers and cells in culture it has
been proposed that phosphorylation of the regulatory light chain (RLC) of sarcomeric myosin plays a role in
enhancing ventricular contraction while phosphorylation of either sarcomeric or cytoplasmic myosin-IIB
promotes sarcomere assembly. Functional changes in the expression and activity of Ca2+/calmodulin-
dependent myosin light chain kinase (MLCK) may lead to cardiomyopathy. Although cardiac myocytes
contain smooth (sm) muscle MLCK, it is not clear that this is the only kinase responsible for RLC
phosphorylations. We propose to identify the kinase that phosphorylates the respective RLCs in addition to
physiological roles for RLC phosphorylations in cardiac contraction and sarcomere assembly. Specific Aim
1. Determine effects of overexpression and knockout of smMLCK in ventricular and atrial myocytes.
Transgenic mice will be made with MLCK expressed specifically in cardiac myocytes. The gene for smooth
muscle MLCK will be ablated by crossing mice with the floxed smooth muscle MLCK gene and mice
expressing Cre specifically in cardiac myocytes. Other kinases that phosphorylate RLC will be identified.
RLC phosphorylations will be measured in cardiac tissues as well as isolated myocytes. Specific Aim 2.
Determine if functional consequences are associated with changes in expression of MLCK isoforms.
Anatomical properties of hearts from transgenic and knockout mice will be assessed. Functional properties
including contractile indices will be measured in perfused hearts and in vivo by invasive and noninvasive
measurements. Responsiveness to stresses that lead to cardiac hypertrophy will also be evaluated.
Specific Aim 3. Determine if sarcomere assembly is affected by overexpression or knockout of smMLCK.
Sarcomere formation in response to hypertrophic agents will be measured in myocytes from newborn
transgenic or knockout mice. Morphometric analyses will be combined with RLC phosphorylation
measurements. Development of myofibrillar structure will be examined in hearts from embryonic knockout
mice. Results from these studies will provide novel biochemical insights into the physiological regulation and
functional importance of cardiac myosin light chain phosphorylation.
心肌收缩是肌凝蛋白与肌动蛋白循环相互作用的结果
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JAMES T STULL其他文献
JAMES T STULL的其他文献
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{{ truncateString('JAMES T STULL', 18)}}的其他基金
Signal transduction mechanisms to myosin phosphatase
肌球蛋白磷酸酶的信号转导机制
- 批准号:
8436884 - 财政年份:2013
- 资助金额:
$ 38.11万 - 项目类别:
Signal transduction mechanisms to myosin phosphatase
肌球蛋白磷酸酶的信号转导机制
- 批准号:
8989145 - 财政年份:2013
- 资助金额:
$ 38.11万 - 项目类别:
Roles of Myosin Light Chain Kinases in the Heart
肌球蛋白轻链激酶在心脏中的作用
- 批准号:
7760983 - 财政年份:2006
- 资助金额:
$ 38.11万 - 项目类别:
Roles of Myosin Light Chain Kinases in the Heart
肌球蛋白轻链激酶在心脏中的作用
- 批准号:
7033144 - 财政年份:2006
- 资助金额:
$ 38.11万 - 项目类别:
Roles of Myosin Light Chain Kinases in the Heart
肌球蛋白轻链激酶在心脏中的作用
- 批准号:
7171824 - 财政年份:2006
- 资助金额:
$ 38.11万 - 项目类别:
Roles of Myosin Light Chain Kinases in the Heart
肌球蛋白轻链激酶在心脏中的作用
- 批准号:
7350160 - 财政年份:2006
- 资助金额:
$ 38.11万 - 项目类别:
NEURONAL NITRIC OXIDE SYNTHASE IN SKELETAL MUSCLE
骨骼肌中的神经元一氧化氮合酶
- 批准号:
6323364 - 财政年份:2000
- 资助金额:
$ 38.11万 - 项目类别:
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肌动蛋白和肌动蛋白结合蛋白的结构/相互作用
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