Collaboration of AMPK and PKC to induce phosphorylation of Ser413 on PIP5K1B resulting in decreased kinase activity and reduced PtdIns(4,5)P2 synthesis in response to oxidative stress and energy restriction.
Authorsvan den Bout, Iman
Jones, David R
Shah, Zahid H
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AbstractThe spatial and temporal regulation of the second messenger PtdIns(4,5)P2 has been shown to be crucial for regulating numerous processes in the cytoplasm and in the nucleus. Three isoforms of PIP5K1 (phosphatidylinositol 4-phosphate 5-kinase), A, B and C, are responsible for the regulation of the major pools of cellular PtdIns(4,5)P2. PIP5K1B is negatively regulated in response to oxidative stress although it remains unclear which pathways regulate its activity. In the present study, we have investigated the regulation of PIP5K1B by protein phosphorylation. Using MS analysis, we identified 12 phosphorylation sites on PIP5K1B. We developed a phospho-specific antibody against Ser413 and showed that its phosphorylation was increased in response to treatment of cells with phorbol ester, H2O2 or energy restriction. Using inhibitors, we define a stress-dependent pathway that requires the activity of the cellular energy sensor AMPK (AMP-activated protein kinase) and PKC (protein kinase C) to regulate Ser413 phosphorylation. Furthermore, we demonstrate that PKC can directly phosphorylate Ser413 in vitro. Mutation of Ser413 to aspartate to mimic serine phosphorylation decreased both PIP5K1B activity in vitro and PtdIns(4,5)P2 synthesis in vivo. Our studies show that collaboration between AMPK and PKC dictates the extent of Ser413 phosphorylation on PIP5K1B and regulates PtdIns(4,5)P2 synthesis.
CitationCollaboration of AMPK and PKC to induce phosphorylation of Ser413 on PIP5K1B resulting in decreased kinase activity and reduced PtdIns(4,5)P2 synthesis in response to oxidative stress and energy restriction. 2013, 455 (3):347-58 Biochem J
- Both phosphatidylinositol 3-kinase and phosphatidylinositol 4-kinase products are increased by antigen receptor signaling in B cells.
- Authors: Gold MR, Aebersold R
- Issue date: 1994 Jan 1
- Oxidants depress the synthesis of phosphatidylinositol 4,5-bisphosphate in heart sarcolemma.
- Authors: Mesaeli N, Tappia PS, Suzuki S, Dhalla NS, Panagia V
- Issue date: 2000 Oct 1
- A role for PtdIns(4,5)P2 and PIP5Kalpha in regulating stress-induced apoptosis.
- Authors: Halstead JR, van Rheenen J, Snel MH, Meeuws S, Mohammed S, D'Santos CS, Heck AJ, Jalink K, Divecha N
- Issue date: 2006 Sep 19
- PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions.
- Authors: van den Bout I, Divecha N
- Issue date: 2009 Nov 1
- Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P2 pools.
- Authors: Santarius M, Lee CH, Anderson RA
- Issue date: 2006 Aug 15