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| Subject Categories: Signal Transduction |
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| The EMBO Journal
(2004) 23, 3031–3040, doi:10.1038/sj.emboj.7600321 Published online 15 July 2004 |
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| PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate |
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| Sandra C Pierre, Julia Häusler, Kerstin Birod, Gerd Geisslinger and Klaus Scholich |
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Pharmazentrum frankfurt, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt, Germany To whom correspondence should be addressed Klaus Scholich, Pharmazentrum frankfurt, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Tel.: +49 69 6301 83103; Fax: +49 69 6301 83378; E-mail: scholich@em.uni-frankfurt.de Received 26 March 2004; Accepted 21 June 2004; Published online 15 July 2004. |
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| Abstract |
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| PAM (Protein Associated with Myc) is an almost ubiquitously expressed protein that is one of the most potent inhibitors of adenylyl cyclase activity known so far. Here we show that PAM is localized at the endoplasmic reticulum in HeLa cells and that upon serum treatment PAM is recruited to the plasma membrane, causing an inhibition of adenylyl cyclase activity. We purified the serum factor that induced PAM translocation and identified it as sphingosine-1-phosphate (S1P). Within 15 min after incubation with S1P, PAM appeared at the plasma membrane and was detectable for up to 120 min. Sphingosine-1-phosphate induced adenylyl cyclase inhibition in two phases: an initial (1–10 min) and a late (20–240 min) phase. The initial adenylyl cyclase inhibition was Gi-mediated and PAM independent. In the late phase, adenylyl cyclase inhibition was PAM dependent and attenuated cyclic AMP (cAMP) signaling by various cAMP-elevating signals. This makes PAM the longest lasting nontranscriptional regulator of adenylyl cyclase activity known to date and presents a novel mechanism for the temporal regulation of cAMP signaling. |
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| Keywords: adenylyl cyclase, cAMP, inhibitory G protein, PAM, sphingosine-1-phosphate |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHDifferential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes Nature Letters to Editor (04 Aug 1988) |
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