由成纤维细胞生长因子1在表达MDA - MB - 231 mRNA的非洲爪蟾卵母细胞上引发的转导级联反应。生长因子受体结合蛋白2、磷脂酰肌醇3激酶、Src酪氨酸激酶和磷脂酶Cγ的作用

Transduction cascades initiated by fibroblast growth factor 1 on Xenopus oocytes expressing MDA-MB-231 mRNAs. Role of Grb2, phosphatidylinositol 3-kinase, Src tyrosine kinase, and phospholipase Cgamma.

作者信息

Browaeys-Poly E, Cailliau K, Vilain J P

机构信息

Université des Sciences et Technologies de Lille, Laboratoire de Biologie du Développement, UPRES EA 1033, Bâtiment SN3, Cedex 59655, Villeneuve d'Ascq, France.

出版信息

Cell Signal. 2001 May;13(5):363-8. doi: 10.1016/s0898-6568(01)00149-8.

DOI:10.1016/s0898-6568(01)00149-8

PMID:11369518

Abstract

Xenopus oocytes expressing fibroblast growth factor receptors (FGFRs) from the hormone-independent breast cancer cells, MDA-MB-231, are used as a biological system to analyze the signalling cascades initiated by FGF1. FGF1 induces ERK2 phosphorylation and G2/M transition. These events are dependent on the Shc/Grb2/Ras pathway, on Src and PI3Kinase (PI3K), as shown by the use of SH2 domains or dominant negative proteins, and on PLC gamma and calcium as demonstrated by a PLC gamma inhibitory peptide and BAPTA-AM. FGF1 mobilizes Ins(1,4,5)P3-sensitive calcium stores, as recorded through the inhibition by caffeine of a chloride calcium-dependent current in expressing oocytes. This study shows that the transduction cascades induced by FGF1 on FGFRs from MDA-MB-231 cells represent the sum of Ras, Src, PI3K, and PLC gamma pathways. It emphasizes the mitogenic effect of the PLC gamma-calcium cascade.

摘要

表达来自激素非依赖性乳腺癌细胞MDA-MB-231的成纤维细胞生长因子受体（FGFRs）的非洲爪蟾卵母细胞被用作一种生物系统，以分析由FGF1启动的信号级联反应。FGF1诱导ERK2磷酸化和G2/M期转换。如使用SH2结构域或显性负性蛋白所表明的，这些事件依赖于Shc/Grb2/Ras途径、Src和磷脂酰肌醇-3激酶（PI3K），并且如PLCγ抑制肽和BAPTA-AM所证明的，依赖于PLCγ和钙。FGF1可动员Ins(1,4,5)P3敏感的钙库，这是通过咖啡因对表达卵母细胞中氯钙依赖性电流的抑制作用来记录的。本研究表明，FGF1在MDA-MB-231细胞的FGFRs上诱导的转导级联反应代表了Ras、Src、PI3K和PLCγ途径的总和。它强调了PLCγ-钙级联反应的促有丝分裂作用。