Regulation of Ras-Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
基本信息
- 批准号:7733001
- 负责人:
- 金额:$ 51.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AllelesAreaBiochemicalCell ProliferationColorectalColorectal CancerEventFamilyFamily memberGoalsHumanLinkLung AdenocarcinomaMEKsMalignant NeoplasmsMalignant neoplasm of pancreasMammalian CellMissionMutationOncogenicOvarianPapillary thyroid carcinomaPathway interactionsPhosphorylationProcessProtein KinaseProtein-Serine-Threonine KinasesProteinsProto-Oncogene Proteins B-rafReceptor Protein-Tyrosine KinasesRegulationResearchSignal TransductionSignal Transduction PathwayTherapeuticTherapeutic InterventionThyroid carcinomaanticancer researchcell transformationdesignmelanomamemberpreventraf Kinasestumortumorigenesis
项目摘要
The Ras pathway is a critical signal transduction cascade involved in regulating cellular proliferation, differentiation, and survival. Members of the Raf serine/threonine kinase family are key intermediates in this pathway, functioning to relay signals from activated Ras to the downstream protein kinases, MEK and ERK. Three Raf proteins are found in mammalian cells, Raf-1, A-Raf, and B-Raf. As might be expected for proteins so centrally involved in cell signaling, the Raf kinases also contribute to oncogenic transformation and cancer. For example, mutation or amplification of upstream regulators of Raf, such as receptor tyrosine kinases and Ras, frequently induces deregulated signaling through the Raf/MEK/ERK cascade in tumors harboring these alleles. Moreover, constitutively active Raf proteins can themselves cause cell transformation. In particular, mutation of the B-Raf family member is observed in 67% of malignant melanomas as well as in many colorectal, ovarian, and papillary thyroid carcinomas. During this past fiscal year, our research identified CK2 as an upstream protein kinase that contributes to Raf activation. Our studies have also revealed that the oncogenic potential of the B-Raf kinase can be altered by specific phosphorylation events and protein interactions. Together, these findings identify potential targets for therapeutic intervention in tumors with constitutive Ras- or Raf-dependent signaling.
Ras通路是参与调节细胞内信号转导的关键信号转导级联。 细胞增殖、分化和存活。Raf丝氨酸/苏氨酸成员 激酶家族是该途径中关键中间体,其功能是从 激活Ras至下游蛋白激酶MEK和ERK。三种Raf蛋白被发现在 哺乳动物细胞、Raf-1、A-Raf和B-Raf。正如我们所预期的那样, Raf激酶参与细胞信号传导,也有助于致癌转化, 癌例如,Raf的上游调节因子如受体的突变或扩增, 酪氨酸激酶和Ras,经常通过Raf/MEK/ERK诱导失调的信号传导 携带这些等位基因的肿瘤中的级联反应。此外,组成型活性Raf蛋白可以 它们本身会引起细胞转化。特别地,B-Raf家族成员的突变是 在67%的恶性黑色素瘤以及许多结直肠、卵巢和乳头状瘤中观察到 甲状腺癌在过去的一个财政年度,我们的研究确定CK 2为上游 促进Raf激活的蛋白激酶。我们的研究还表明, B-Raf激酶的致癌潜力可以通过特定的磷酸化事件改变, 蛋白质相互作用总之,这些发现确定了治疗的潜在靶点。 用组成型Ras或Raf-dependent信号转导干预肿瘤。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Inhibition of lysophosphatidic acid acyltransferase beta disrupts proliferative and survival signals in normal cells and induces apoptosis of tumor cells.
抑制溶血磷脂酸酰基转移酶β会破坏正常细胞的增殖和生存信号,并诱导肿瘤细胞凋亡。
- DOI:
- 发表时间:2003
- 期刊:
- 影响因子:5.7
- 作者:Coon,Michael;Ball,Alexey;Pound,Jeannine;Ap,Sophe;Hollenback,David;White,Thayer;Tulinsky,John;Bonham,Lynn;Morrison,DeborahK;Finney,Robert;Singer,JackW
- 通讯作者:Singer,JackW
KSR regulation of the Raf-MEK-ERK cascade.
Raf-MEK-ERK 级联的 KSR 调节。
- DOI:10.1016/s0076-6879(05)07019-9
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Ritt,DanielA;Daar,IraO;Morrison,DeborahK
- 通讯作者:Morrison,DeborahK
Cancer: enzymes play molecular tag.
癌症:酶发挥分子标签作用。
- DOI:10.1038/428813a
- 发表时间:2004
- 期刊:
- 影响因子:64.8
- 作者:Morrison,DeborahK
- 通讯作者:Morrison,DeborahK
HDM2 phosphorylation by MAPKAP kinase 2.
MAPKAP 激酶 2 使 HDM2 磷酸化。
- DOI:10.1038/sj.onc.1208389
- 发表时间:2005
- 期刊:
- 影响因子:8
- 作者:Weber,HansOliver;Ludwig,RobertL;Morrison,Deborah;Kotlyarov,Alexey;Gaestel,Matthias;Vousden,KarenH
- 通讯作者:Vousden,KarenH
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DEBORAH K MORRISON其他文献
DEBORAH K MORRISON的其他文献
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{{ truncateString('DEBORAH K MORRISON', 18)}}的其他基金
INTERACTIONS OF PP60 C-SRC WITH POLYOMA MIDDLE T ANTIGEN
PP60 C-SRC 与多瘤中 T 抗原的相互作用
- 批准号:
3033022 - 财政年份:1988
- 资助金额:
$ 51.95万 - 项目类别:
INTERACTIONS OF PP60 C-SRC WITH POLYOMA MIDDLE T ANTIGEN
PP60 C-SRC 与多瘤中 T 抗原的相互作用
- 批准号:
3033021 - 财政年份:1987
- 资助金额:
$ 51.95万 - 项目类别:
REGULATION OF RAS DEPENDENT SIGNAL TRANSDUCTION PATHWAYS
RAS 依赖性信号转导途径的调节
- 批准号:
6419915 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
Regulation of Ras-Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
- 批准号:
7338463 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
Regulation of Ras-Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
- 批准号:
6951343 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
Regulation of Ras-Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
- 批准号:
6763545 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
Regulation of Ras-Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
- 批准号:
7291711 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
Regulation of Ras Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
- 批准号:
6559212 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
Regulation of Ras-Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
- 批准号:
7052419 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
Regulation of Ras-Dependent Signal Transduction Pathways
Ras 依赖性信号转导途径的调节
- 批准号:
7592665 - 财政年份:
- 资助金额:
$ 51.95万 - 项目类别:
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