In response to oxidative stress and energy restriction AMPK and PKC collaborate to induce the phosphorylation of Serine 413 on PIP5K1B resulting in decreased kinase activity and reduced PtdIns(4,5)P2 synthesis

In this study we have investigated the regulation of PIP5K1B by protein phosphorylation. Using mass spectrometric analysis we identified 12 phosphorylation sites on PIP5K1B. We developed a phospho-specific antibody to S413 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 AMP-Kinase (AMPK) and Protein Kinase C (PKC) to regulate S413 phosphorylation. Furthermore, we demonstrate that PKC can directly phosphorylate S413 in vitro. Mutation of S413 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 S413 phosphorylation on PIP5K1B and regulates PtdIns(4,5)P2synthesis.

Source: BJ Cell - August 5, 2013 Category: Biochemistry Authors: I van den Bout, D R Jones, Z H Shah, J R Halstead, W Keune, S Mohammed, C S D'Santos, N Divecha Tags: BJ Signal Source Type: research