Atypical MAP Kinase Signal Transduction
Atypical MAP Kinase Signal Transduction
批准号:
10577709
负责人:
JEFFREY A HADWIGER
金额:
$43.62万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
未结题
起止时间:
2019-03-08 至 2025-08-31
关键词:
Amoeba genusAnimal ModelAnimalsBinding ProteinsBiological AssayCell Fate ControlCell NucleusCellsChemotaxisCo-ImmunoprecipitationsCollaborationsCyclic AMPCytoplasmDevelopmentDictyosteliumDictyostelium discoideumDockingEukaryotaEukaryotic CellFolic AcidFundingG-Protein-Coupled ReceptorsGTP-Binding ProteinsGene ExpressionGeneticImmune responseLeadMammalsMapsMass Spectrum AnalysisMediatingMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesModificationMovementOrganismOrthologous GenePhosphorylationPhosphotransferasesProtein KinaseProteinsReceptor Protein-Tyrosine KinasesRegulationResearchRoleSignal PathwaySignal TransductionSignal Transduction PathwaySiteSpecificityTestingbasebiochemical toolscell growthcell motilityfungusgenetic analysisgenetic regulatory proteinhuman diseasein vivoinsightmutantresponsetranscription factor
中文摘要
项目总结:
MAPK是许多信号转导的调节成分
影响真核细胞生长、分化和运动的途径。相对的
人们对非典型MAPK的功能和调控知之甚少
哺乳动物中的MAPK15/Erk8)仅在具有细胞运动性的真核生物中发现。非典型
MAPK不被传统的MAPK激酶激活,而外部信号
触发激活是未知的,除了模式生物Dictyostelius的阿米巴
用于趋化运动和发育。我们发现Dictyostelius
非典型的MAPK,ERK2,对多种信号的趋化运动是必不可少的。在我们的
我们之前资助的研究还发现ERK2可以磷酸化特定的
GATA转录因子GTAC的残基导致该因子的易位
从细胞核到细胞质,对至少两个趋化信号做出反应
促进不同的细胞命运。我们还证明了ERK2的活性并不是
体内激活所需,表明非传统的MAPK激酶调节
非典型的MAPK,而不是自动磷酸化。拟议的研究将
研究ERK2是否通过差异性修饰促进不同的细胞命运
GTAC或通过调节其他转录因子。我们将使用标记为GFP的
GTAC绘制ERK2对接地点地图,并将这些地点与其他组的对接地点进行比较
MAPK。我们还将使用免疫共沉淀、质谱学和基因
分析鉴定信号通路中与ERK2相关并发挥作用的蛋白质
并确定直接调节ERK2激活的蛋白质。这个项目的成果是
期望确定非典型MAPK调节和功能的具体机制和
揭示非典型MAPK信号在趋化运动和细胞命运中的作用
可以指导其他生物体中MAPK研究的测定,如
哺乳动物。
英文摘要
Project Summary:
MAP kinases (MAPKs) are regulatory components of many signal transduction
pathways that impact eukaryotic cell growth, differentiation, and movement. Relatively
little is known about the function and regulation of atypical MAPKs (represented by
MAPK15/Erk8 in mammals) found only in eukaryotes that have cell motility. Atypical
MAPKs are not activated by conventional MAPK kinases and the external signals that
trigger activation are not known except in the amoeba Dictyostelium, a model organism
for chemotactic movement and development. We have found that the Dictyostelium
atypical MAPK, Erk2, is essential for chemotactic movement to multiple signals. In our
previously funded research we also discovered that Erk2 phosphorylates specific
residues of a GATA transcription factor, GtaC, resulting in the translocation of this factor
from the nucleus to the cytoplasm in response to at least two chemotactic signals that
promote different cell fates. We have also demonstrated that Erk2 kinase activity is not
required for activation in vivo indicating that an unconventional MAPK kinase regulates
atypical MAPKs rather than autophosphorylation. The proposed research will
investigate if Erk2 promotes different cell fates through the differentially modification of
GtaC or through the regulation of other transcription factors. We will use a GFP tagged
GtaC to map Erk2 docking sites and compare these to docking sites of other groups of
MAPKs. We will also use co-immunoprecipitations, mass spectrometry, and genetic
analysis to identify proteins that associate and function with Erk2 in signaling pathways
and identify proteins that directly regulate Erk2 activation. The results of this project are
expected to identify specific mechanisms of atypical MAPK regulation and function and
uncover roles for atypical MAPK signaling in chemotactic movement and cell fate
determination that can guide the research of MAPKs in other organisms such as
mammals.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.cellsig.2021.110117
发表时间:
2021-11
期刊:
Cellular signalling
影响因子:
4.8
作者:
[Adhikari N, McGill IN, Hadwiger JA]
通讯作者:
Hadwiger JA
Atypical MAP Kinase Signal Transduction
-
批准号:9906396
-
项目类别:
-
资助金额:$4.42万
-
财政年份:2019
-
负责人:JEFFREY A HADWIGER
-
依托单位:
Role of STAT proteins in MAPK signal transduction pathways
-
批准号:8101669
-
项目类别:
-
资助金额:$27.61万
-
财政年份:2011
-
负责人:JEFFREY A HADWIGER
-
依托单位:
G Protein-Mediated Gene Regulation
-
批准号:7434755
-
项目类别:
-
资助金额:$2.31万
-
财政年份:2005
-
负责人:JEFFREY A HADWIGER
-
依托单位:
G Protein-Mediated Gene Regulation
-
批准号:6898083
-
项目类别:
-
资助金额:$22.11万
-
财政年份:2005
-
负责人:JEFFREY A HADWIGER
-
依托单位:
海外基金