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
项目概要:
MAP激酶(MAPKs)是许多信号转导的调节组分
影响真核细胞生长、分化和运动的途径。相对
关于非典型MAPK的功能和调节知之甚少(由
MAPK 15/Erk 8在哺乳动物中)仅在具有细胞运动性的真核生物中发现。非典型
MAPK不被常规的MAPK激酶激活,
触发激活是未知的,除了在阿米巴Dictyosteoba,模式生物
用于趋化运动和发育。我们发现网骨藻
非典型MAPK,Erk 2,对于多种信号的趋化运动是必需的。在我们
之前资助的研究,我们还发现Erk 2磷酸化特异性,
加塔转录因子GtaC的残基,导致该因子易位
从细胞核到细胞质,以响应至少两种趋化信号,
促进不同的细胞命运。我们还证明Erk 2激酶活性不是
这表明非常规MAPK激酶调节
非典型MAPK而不是自身磷酸化。拟议的研究将
研究Erk 2是否通过差异修饰促进不同的细胞命运,
GtaC或通过其他转录因子的调节。我们将使用GFP标记
GtaC绘制Erk 2对接位点,并将其与其他组的对接位点进行比较。
MAPKs我们还将使用免疫共沉淀、质谱和遗传学方法,
分析以鉴定在信号传导途径中与Erk 2相关并起作用的蛋白质
并鉴定直接调节Erk 2激活的蛋白质。该项目的成果是
期望确定非典型MAPK调节和功能的特定机制,
揭示非典型MAPK信号在趋化运动和细胞命运中的作用
这一确定可以指导其他生物体中MAPK的研究,
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