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The Coffin–Lowry Syndrome‐associated Protein RSK2 Controls Neuroendocrine Secretion through the Regulation of Phospholipase D1 at the Exocytotic Sites
Author(s) -
ZeniouMeyer Maria,
Béglé Aurélie,
Bader MarieFrance,
Vitale Nicolas
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2008.04001.x
Subject(s) - exocytosis , phospholipase d , microbiology and biotechnology , secretion , phosphatidic acid , phosphorylation , biology , pld2 , phospholipase c , chemistry , signal transduction , biochemistry , phospholipid , membrane
Together with the soluble N ‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) proteins, fusogenic cone‐shaped lipids, such as phosphatidic acid (PA), have been recently shown to be important actors in membrane fusion during exocytosis. Phospholipase D (PLD) appears to be the main provider of PA at the exocytotic site in neuroendocrine cells. We show here that ribosomal S6 kinase 2 (RSK2) stimulates PLD activity through the phosphorylation of Thr147 in the PLD1 amino‐terminal Phox‐homology domain. In PC12 cells, depletion of RSK2 dramatically prevents PA synthesis at exocytotic sites and inhibits hormone release. Expression of PLD1 phosphomimetic mutants fully restores secretion in cells depleted of RSK2, suggesting that RSK2 is a critical upstream signaling element in the activation of PLD1 to produce the lipids required for exocytosis.