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CELL TRANSFORMATION BY INSULIN AND IGF1 RECEPTORS

胰岛素和 IGF1 受体的细胞转化

基本信息

批准号：
6475785
负责人：
LU-HAI WANG
金额：
$ 29.47万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-06-01 至 2003-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6475785
关键词：
G protein biological signal transduction cell growth regulation cell line cell transformation contact inhibition growth factor receptors insulin receptor insulinlike growth factor mutant oncoproteins phosphatidylinositol 3 kinase transfection yeast two hybrid system

项目摘要

The goal of the proposed study is to elucidate signal transduction pathways that are important in mediating the oncogenic insulin and insulin-like growth factor I receptors (IR and IGFR)-induced cell growth and transformation, and to explore novel signaling molecules for these receptors. IR and IGFR are two receptor tyrosine kinases which play important roles in regulating cellular metabolic activities, growth and differentiation. The focus will be on identifying the specific Rho/Rac/Cdc42-mediated signaling pathways and molecules involved in regulating distinct cell transforming properties. The major approach will employ loss-of-function mutants of the oncogenic IR and IGFR, as well as various activated and dominant inhibitory mutants of the signaling molecules of Rho/Rac/Cdc42, IRS-1 and P13 kinase to dissect their signal transduction pathways important for cell growth and transformation. The specific aims are: 1. To investigate the effect of oncogenic IR and IGFR and their loss-of-function mutants on Rho/Rac/Cdc42-mediated signaling functions. 2. To elucidate the Rho/Rac/Cdc42-mediated signaling pathways involved in regulating the oncogenic IR and IGFR-induced cell growth and transformation. 3. To explore the role of IRS-1 and P13 kinase in the oncogenic IR and IGFR- induced cell growth and transformation. 4. To explore the role of an IGFR-interacting G beta-related protein, named IGIP, in IGFR signaling functions.

这项研究的目的是阐明信号转导在介导致癌胰岛素中起重要作用的途径，胰岛素样生长因子I受体（IR和IGFR）诱导的细胞生长和转化，并探索新的信号分子，受体。 IR和IGFR是两种受体酪氨酸激酶，在调节细胞代谢活动、生长和分化重点将是确定具体的 Rho/Rac/Cdc 42介导的信号通路和参与的分子调节不同的细胞转化特性。主要方法将使用致癌IR和IGFR的功能丧失突变体，以及各种激活和显性抑制突变体的 Rho/Rac/Cdc 42、IRS-1和P13激酶的信号分子，以解剖它们的信号转导途径对细胞生长和转型具体目标是：1.探讨了影响致癌IR和IGFR及其功能丧失突变体， Rho/Rac/Cdc 42介导的信号传导功能。 2.阐明本 Rho/Rac/Cdc 42介导的信号通路参与调节细胞凋亡。致癌IR和IGFR诱导的细胞生长和转化。 3.到探讨IRS-1和P13激酶在癌基因IR和IGFR中的作用。诱导细胞生长和转化。 4.为了探索一个 IGFR相互作用的G β相关蛋白，命名为IGIP，在IGFR信号传导中功能协调发展的

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Distinctive effects of the carboxyl-terminal sequence of the insulin-like growth factor I receptor on its signaling functions.

胰岛素样生长因子 I 受体的羧基末端序列对其信号传导功能的独特影响。

DOI：
10.1128/jvi.67.11.6835-6840.1993
发表时间：
1993
期刊：
Journal of virology
影响因子：
5.4
作者：
Liu,D;Zong,CS;Wang,LH
通讯作者：
Wang,LH

Ala-->Gly mutation in the putative catalytic loop confers temperature sensitivity on Ros, insulin receptor, and insulin-like growth factor I receptor protein-tyrosine kinases.

假定催化环中的 Ala-->Gly 突变赋予 Ros、胰岛素受体和胰岛素样生长因子 I 受体蛋白酪氨酸激酶温度敏感性。

DOI：
10.1073/pnas.91.1.321
发表时间：
1994
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Chen,J;Hanafusa,T;Wang,LH
通讯作者：
Wang,LH

Differential requirements of the MAP kinase and PI3 kinase signaling pathways in Src- versus insulin and IGF-1 receptors-induced growth and transformation of rat intestinal epithelial cells.

Src- 与胰岛素和 IGF-1 受体诱导的大鼠肠上皮细胞生长和转化中 MAP 激酶和 PI3 激酶信号通路的不同需求。