2. Academic Validation
  3. A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase

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

  • Nat Cell Biol. 2001 Nov;3(11):1020-4. doi: 10.1038/ncb1101-1020.
M Schmidt 1,  S Evellin,  P A Weernink,  F von Dorp,  H Rehmann,  J W Lomasney,  K H Jakobs
Affiliations

Affiliation

  • 1 Institut für Pharmakologie, Universitätsklinikum Essen, 45122 Essen, Germany. martina.schmidt@uni-essen.de
PMID: 11715024 DOI: 10.1038/ncb1101-1020
Abstract

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. 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 beta2-adrenoceptor expressed in HEK-293 cells or the endogenous receptor for prostaglandin E1 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, and involve the recently identified PLC-epsilon isoform.

Figures