Protein Kinase Novel 2 (PKN2) in heart

心脏中的蛋白激酶 Novel 2 (PKN2)

基本信息

  • 批准号:
    10548141
  • 负责人:
  • 金额:
    $ 54.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-01-01 至 2024-12-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY The Protein Kinase Novel (PKNs) family of kinases, also known as Protein Kinase C-related kinases, belong to the PKC superfamily. A single nucleotide polymorphism at the Pkn2 locus is associated with greater risk for coronary artery disease/myocardial infarction, and elevated levels of PKN2 protein are associated with heart disease, highlighting the importance of PKN2 in heart. Global deletion of Pkn2 in mouse results in lethality at embryonic day (E) 10 with cardiac defects. Conditional deletion of Pkn2, utilizing SM22α-Cre mice, results in partial lethality between E13.5 and weaning, with surviving mutants displaying abnormal cardiac phenotypes. These observations strongly suggest that PKN2 plays a critical role in the developing heart, however, because SM22α-Cre is expressed not only in early developing cardiomyocytes, but also in smooth muscle, skeletal muscle, and myeloid and lymphoid immune cells, this previous study does not address the cardiomyocyte- specific requirement. Intriguingly, a recent study showed that deletion of Pkn1 and Pkn2 in adult cardiomyocytes, utilizing αMHC-MerCreMer mice, did not affect basal cardiac function, but protected mice from pressure overload- and angiotensin II-induced cardiac hypertrophy and heart failure, suggesting that PKN inactivation could be a unique therapeutic target for heart failure. The contradiction between the partial embryonic lethality of SM22α-Cre:Pkn2 knockout mice and protective effects observed in adult αMHC- MerCreMer:Pkn1/2 double knockout mice highlights a critical need to define potential roles of PKN2 in cardiomyocytes at different developmental stages. To address this contradiction, we have generated novel Pkn2 cardiomyocyte-specific constitutive knockout (cKO) and Pkn2 tamoxifen-inducible cardiomyocyte-specific knockout (icKO) mouse models utilizing Xmlc2-Cre and Tnnt2-MerCreMer mouse lines, respectively. Upon preliminary characterization, Pkn2 cKO mice displayed partial postnatal lethality and cardiac morphological defects as early as E12.5. Echocardiographic studies of surviving mutants revealed a dilated cardiomyopathy phenotype in Pkn2 cKO mutants at both 1 and 3 months of age. In contrast to published reports that loss of Pkn2 in adult cardiomyocytes does not affect basal cardiac function, our preliminary observations suggest that Pkn2 deficiency in developing cardiomyocytes is detrimental. Taken together, the above evidence leads us to the hypothesis that PKN2 plays distinct roles at different stages of cardiomyocyte development through the phosphoregulation of specific substrates. Accordingly, our specific aims are: 1. To elucidate the role of PKN2 in cardiomyocytes by analysis of cardiac and cardiomyocyte structure and function in Pkn2 cKO mice, and to identify endogenous substrates of PKN2 in cardiomyocytes by utilizing unbiased phosphoproteomics and a chemical-genetics approach with an analog-sensitive PKN2 mutant, and 2. To determine the cardiomyocyte- specific requirement for PKN2 in postnatal development by analysis of Pkn2 icKO mice.
项目总结

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Ju Chen其他文献

Ju Chen的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Ju Chen', 18)}}的其他基金

ATF4 a Novel Regulator of Cardiac Development
ATF4 心脏发育的新型调节剂
  • 批准号:
    10657081
  • 财政年份:
    2023
  • 资助金额:
    $ 54.24万
  • 项目类别:
Novel function of a mitochondria phosphatase in cardiac development
线粒体磷酸酶在心脏发育中的新功能
  • 批准号:
    10436945
  • 财政年份:
    2021
  • 资助金额:
    $ 54.24万
  • 项目类别:
Protein Kinase Novel 2 (PKN2) in heart
心脏中的蛋白激酶 Novel 2 (PKN2)
  • 批准号:
    10322445
  • 财政年份:
    2021
  • 资助金额:
    $ 54.24万
  • 项目类别:
Nuclear envelope protein LEMD2 in heart
心脏中的核膜蛋白 LEMD2
  • 批准号:
    10278926
  • 财政年份:
    2021
  • 资助金额:
    $ 54.24万
  • 项目类别:
Nuclear envelope protein LEMD2 in heart
心脏中的核膜蛋白 LEMD2
  • 批准号:
    10662287
  • 财政年份:
    2021
  • 资助金额:
    $ 54.24万
  • 项目类别:
Novel function of a mitochondria phosphatase in cardiac development
线粒体磷酸酶在心脏发育中的新功能
  • 批准号:
    10181409
  • 财政年份:
    2021
  • 资助金额:
    $ 54.24万
  • 项目类别:
Novel function of a mitochondria phosphatase in cardiac development
线粒体磷酸酶在心脏发育中的新功能
  • 批准号:
    10687847
  • 财政年份:
    2021
  • 资助金额:
    $ 54.24万
  • 项目类别:
Nuclear envelope protein LEMD2 in heart
心脏中的核膜蛋白 LEMD2
  • 批准号:
    10463758
  • 财政年份:
    2021
  • 资助金额:
    $ 54.24万
  • 项目类别:
PRDM16 in cardiac development
PRDM16 在心脏发育中的作用
  • 批准号:
    10025986
  • 财政年份:
    2020
  • 资助金额:
    $ 54.24万
  • 项目类别:
PRDM16 in cardiac development
PRDM16 在心脏发育中的作用
  • 批准号:
    10242912
  • 财政年份:
    2020
  • 资助金额:
    $ 54.24万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 54.24万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了