Journal
NATURE CELL BIOLOGY
Volume 3, Issue 11, Pages 1020-1024Publisher
MACMILLAN PUBLISHERS LTD
DOI: 10.1038/ncb1101-1020
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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).
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