A new phospholipase-C - calcium signalling pathway mediated by cyclic AMP and a Rap GTPase

被引：284

作者：

Schmidt, M ^{[1
]}

Evellin, S

Weernink, PAO

vom Dorp, F

Rehmann, H

Lomasney, JW

Jakobs, KH

机构：

[1] Univ Klinikum Essen, Inst Pharmakol, D-45122 Essen, Germany

[2] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany

[3] UMC Utrecht, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands

[4] UMC Utrecht, Ctr Biomed Genet, NL-3584 CG Utrecht, Netherlands

[5] Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA

[6] Northwestern Univ, Sch Med, Dept Pharmacol, Chicago, IL 60611 USA

来源：

NATURE CELL BIOLOGY | 2001年 / 3卷 / 11期

关键词：

D O I：

10.1038/ncb1101-1020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Stimulation of phosphoinositide-hydrolysing phospholipase C (PLC) generating inositol-1,4,5-trisphosphate is a major calcium signalling pathway used by a wide variety of membrane receptors, activating distinct PLC-beta or PLC-gamma isoforms(1-4). Here we report a new PLC and calcium signalling pathway that is triggered by cyclic AMP (cAMP) and mediated by a small GTPase of the Rap family. Activation of the adenylyl cyclase-coupled beta (2)-adrenoceptor expressed in HEK-293 cells or the endogenous receptor for prostaglandin E-1 in N1E-115 neuroblastoma cells induced calcium mobilization and PLC stimulation, seemingly caused by cAMP formation, but was independent of protein kinase A (PKA). We provide evidence that these receptor responses are mediated by a Rap GTPase, specifically Rap2B, activated by a guanine-nucleotide-exchange factor (Epac) regulated by cAMP(5,6), and involve the recently identified PLC-epsilon isoform(7-9).

引用

页码：1020 / 1024

页数：5

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