权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

IFNAR1 signaling through STAT3, PI-3 kinase and NFkB

通过 STAT3、PI-3 激酶和 NFkB 的 IFNAR1 信号传导

基本信息

批准号：
7161764
负责人：
LAWRENCE MARC PFEFFER
金额：
$ 28.76万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-12-02 至 2008-12-31
项目状态：
已结题

项目摘要

Understanding the molecular basis of interferon-alpha (IFN_) action is an important goal when one considers IFN's therapeutic potential in cancer, viral hepatitis, and multiple sclerosis, as well as its role as a model for understanding cytokine signal transduction. IFNot elicits its biological actions by regulating gene expression through the tyrosine phosphorylation and activation of members of the STAT (signal transducers and activators of transcription) protein family. The applicant found that STAT3, a transcription factor for acute phase response genes, is a critical element in IFN signaling and induction of IFN's biological actions. In addition, it was also found that IFN promotes cell survival by activating NF-KB (nuclear factor-v_B) through a serine kinase-dependent pathway involving PI-3K (phosphatidylinositol-3' kinase) and Akt, as well as STAT3. Based on these findings, the general hypothesis to be tested is that the IFN_x receptor integrates signaling pathways involving STAT3, PI-3K and NF-vJ3. In Specific Aim 1, the role of STAT3 as a transcription factor and an adapter protein for PI-3K will be defined. The proposed studies will determine which specific amino acid residues in STAT3 undergo IFN-dependent phosphorylation, the relationship of these phosphorylation events to the biologic actions of IFN, and which IFN-responsive genes are STAT3- regulated. In Specific Aim 2, the role of NF-vJ3 in IFNa action will be defined. The proposed studies will define the relationship between PI-3K/Akt-mediated phosphorylation events and the anti-apoptotic action of IFN, the roles of TRAFs (TNF receptor-associated factors) and NIK (NF-vJ3-inducing kinase) in IFN- induced NF-rJ3 activation, the role of NF-vJ3 in gene induction by IFN, and the role of the Iv33 kinase complex in IFN promoted NF-KB activation and cell survival. Despite advances made on the IFN_x signaling pathway, the mechanisms that underlie the induction of the different biological actions of IFN_x remain poorly understood. This proposal focuses on characterizing the molecular basis of signaling pathways as they relate to 1FN action on cell proliferation and survival.

了解干扰素- α (IFN_)作用的分子基础是一个重要的目标

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Corticotropin-releasing hormone inhibits nuclear factor-kappaB pathway in human HaCaT keratinocytes.

促肾上腺皮质激素释放激素抑制人 HaCaT 角质形成细胞中的核因子-kappaB 通路。

DOI：
10.1111/j.1523-1747.2003.12612.x
发表时间：
2003
期刊：
The Journal of investigative dermatology
影响因子：
0
作者：
Zbytek,Blazej;Pfeffer,LawrenceM;Slominski,AndrzejT
通讯作者：
Slominski,AndrzejT

Inhibition of ornithine decarboxylase induces STAT3 tyrosine phosphorylation and DNA binding in IEC-6 cells.

DOI：
10.1152/ajpcell.2000.278.2.c331
发表时间：
2000-02
期刊：
American journal of physiology. Cell physiology
影响因子：
0
作者：
L. Pfeffer;C. Yang;S. Pfeffer;A. Murti;S. McCormack;L. Johnson
通讯作者：
L. Pfeffer;C. Yang;S. Pfeffer;A. Murti;S. McCormack;L. Johnson

IFN-beta sensitizes neuroblastoma to the antitumor activity of temozolomide by modulating O6-methylguanine DNA methyltransferase expression.

DOI：
10.1158/1535-7163.mct-08-0806
发表时间：
2008-12
期刊：
Molecular cancer therapeutics
影响因子：
5.7
作者：
Rosati SF;Williams RF;Nunnally LC;McGee MC;Sims TL;Tracey L;Zhou J;Fan M;Ng CY;Nathwani AC;Stewart CF;Pfeffer LM;Davidoff AM
通讯作者：
Davidoff AM

Corticotropin-releasing hormone stimulates NF-kappaB in human epidermal keratinocytes.

促肾上腺皮质激素释放激素刺激人表皮角质形成细胞中的 NF-κB。