IPMK and β-catenin Mediate PLC-β1-dependent Signaling in Myogenic Differentiation

Oncotarget. 2016 Dec 20;7(51):84118-84127. doi: 10.18632/oncotarget.11527.

Abstract

In previous studies, we have reported that phospholipase C (PLC)-β1 plays a crucial role in myogenic differentiation and we determined the importance of its catalytic activity for the initiation of this process. Here we define the effectors that take part to its signaling pathway. We show that the Inositol Polyphosphate Multikinase (IPMK) is able to promote myogenic differentiation since its overexpression determines the up-regulation of several myogenic markers. Moreover, we demonstrate that IPMK activates the same cyclin D3 promoter region targeted by PLC-β1 and that IPMK-induced promoter activation relies upon c-jun binding to the promoter, as we have shown previously for PLC-β1. Furthermore, our data shows that IPMK overexpression causes an increase in β-catenin translocation and accumulation to the nuclei of differentiating myoblasts resulting in higher MyoD activation. Finally, we describe that PLC-β1 overexpression determines too an increase in β-catenin translocation and that PLC-β1, IPMK and β-catenin are mediators of the same signaling pathway since their overexpression results in cyclin D3 and myosin heavy chain (MYH) induction.

Keywords: IPMK; inositol phosphates; myogenic differentiation; phospholipase C-β1; β-catenin.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Blotting, Western
  • Cell Differentiation*
  • Cell Line
  • Cell Nucleus / metabolism
  • Cyclin D3 / genetics
  • Mice
  • Muscle Development / genetics
  • Phospholipase C beta / genetics
  • Phospholipase C beta / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Promoter Regions, Genetic / genetics
  • Signal Transduction / genetics
  • Transcriptional Activation
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Cyclin D3
  • beta Catenin
  • Phosphotransferases (Alcohol Group Acceptor)
  • inositol polyphosphate multikinase
  • Phospholipase C beta