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

Martina Schmidt, Sandrine Evellin, Paschal A.Oude Weernink, Frank vom Dorp, Holger Rehmann, Jon W. Lomasney, Karl H. Jakobs

Research output: Contribution to journalArticlepeer-review

261 Scopus citations

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-β or PLC-γ 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 β2-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-ε isoform.

Original languageEnglish (US)
Pages (from-to)1020-1024
Number of pages5
JournalNature Cell Biology
Volume3
Issue number11
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Cell Biology

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