STRUCTURAL BASIS OF CA2+-CALMODULIN-CALCINEURIN SIGNALLING
STRUCTURAL BASIS OF CA2+-CALMODULIN-CALCINEURIN SIGNALLING
批准号:
8361729
负责人:
Anjana Rao
金额:
$0.18万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-04-01 至 2012-03-31
关键词:
AddressBlood VesselsCalcineurinCalcineurin PathwayCalmodulinClinicalCyclosporineCytokine GeneDevelopmental ProcessFundingGenesGenetic TranscriptionGoalsGrantHeart ValvesHypertrophyImmunosuppressive AgentsIndividualInjuryKineticsMyocardialNational Center for Research ResourcesPharmaceutical PreparationsPhosphoserinePhosphothreoninePrincipal InvestigatorProteinsResearchResearch InfrastructureResourcesRoleSignal TransductionSourceT-Cell ActivationT-LymphocyteTacrolimusTranslatingUnited States National Institutes of HealthVascular Systembasecostgenetic regulatory proteinprotein protein interactionrestenosisstructural biologytranscription factor
中文摘要
这个子项目是利用这些资源的众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
The overall goal of this subproject is to obtain detailed structural and kinetic information on signalling in the Ca2+-calmodulin-calcineurin pathway. Calcineurin (CN) is activated either locally by Ca2+ signals in cellular microdomains or globally by widespread cytoplasmic Ca2+ signals, and controls the activity of other cellular proteins by dephosphorylating specific phosphoserine or phosphothreonine residues.
CN has a prominent role in T cells, where it regulates the transcription factor NFAT and thereby the transcription of cytokine genes and other genes associated with T cell activation. This role of CN is the target of the clinical immunosuppressive drugs cyclosporin A and tacrolimus. CN is also implicated in developmental processes, including the proper formation of cardiac valves and the vascular system, and in pathophysiological changes, including myocardial hypertrophy and vascular restenosis after injury.
This project addresses
(1) how CN signalling is directed through recognition of individual CN substrates;
(2) how CN signalling is directed through interaction with targeting and regulatory proteins;
(3) the conformational changes that initiate and sustain CN activation; and
(4) the kinetics of the conformational changes and protein-protein interactions that translate cytoplasmic Ca signals into CN signalling.
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