ACCELERATED COMMUNICATION EP4 Prostanoid Receptor Coupling to a Pertussis Toxin-Sensitive Inhibitory G Protein
نویسندگان
چکیده
The EP2 and EP4 prostanoid receptor subtypes are G-proteincoupled receptors for prostaglandin E2 (PGE2). Both receptor subtypes are known to couple to the stimulatory guanine nucleotide binding protein (G s) and, after stimulation with PGE2, can increase the formation of intracellular cAMP. In addition, PGE2 stimulation of the EP4 receptor can activate phosphatidylinositol 3-kinase (PI3K) leading to phosphorylation of the extracellular signal-regulated kinases (ERKs) and induction of early growth response factor-1 (EGR-1) (J Biol Chem 278: 12151–12156, 2003). We now report that the PGE2-mediated phosphorylation of the ERKs and induction of EGR-1 can be blocked by pretreatment of EP4-expressing cells with pertussis toxin (PTX). Furthermore, pretreatment with PTX increased the amount of PGE2-stimulated intracellular cAMP formation in EP4-expressing cells but not in EP2-expressing cells. These data indicate that the EP4 prostanoid receptor subtype, but not the EP2, couples to a PTX-sensitive inhibitory G-protein (G i) that can inhibit cAMP-dependent signaling and activate PI3K/ ERK-dependent signaling. Prostaglandin E2 (PGE2) is an endogenous signaling molecule that is produced from arachidonic acid by the sequential actions of cyclooxygenase (COX) and PGE2 synthase. PGE2 is also referred to as a prostanoid, which is a term that encompasses the other prostaglandins (e.g., PGD2 and PGF2 ) and thromboxanes. PGE2 can bind to and stimulate four major prostanoid receptor subtypes that have been named EP1, EP2, EP3, and EP4 (Coleman et al., 1994). These receptors are all seven transmembrane-spanning receptors that activate intracellular second messenger signaling pathways by interacting with heterotrimeric G-proteins. There are four major subfamilies of G-proteins that are defined by their subunits (G ) and by the nature of the signaling pathways they activate (Hepler and Gilman, 1992). Perhaps the most well known are members of the G s and G i subfamilies, whose activation affects the formation of intracellular cAMP by either stimulating or inhibiting the activity of adenylyl cyclase, respectively. Members of the G i subfamily are also known as pertussis toxin (PTX) sensitive G-proteins because they can be inhibited by the actions of this toxin, which is the causative agent of whooping cough. Members of the G q subfamily activate phospholipase C to stimulate inositol phosphate and Ca signaling, whereas members of the G 12 subfamily affect signaling pathways that involve the activation of Rho, a member of the family of small mono-
منابع مشابه
EP(4) prostanoid receptor coupling to a pertussis toxin-sensitive inhibitory G protein.
The EP(2) and EP(4) prostanoid receptor subtypes are G-protein-coupled receptors for prostaglandin E(2) (PGE(2)). Both receptor subtypes are known to couple to the stimulatory guanine nucleotide binding protein (Galpha(s)) and, after stimulation with PGE(2), can increase the formation of intracellular cAMP. In addition, PGE(2) stimulation of the EP(4) receptor can activate phosphatidylinositol ...
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