Convergence of Igf2 expression and adhesion signalling via RhoA and p38 MAPK enhances myogenic differentiation

Fiona A. Lovett, Ivelisse Gonzalez, Dervis A.M. Salih, Laura J. Cobb, Gyanendra Tripathi, Ruth A. Cosgrove, Adele Murrell, Peter J. Kilshaw, Jennifer M. Pell

Research output: Contribution to journalArticlepeer-review

30 Citations (SciVal)


Cell-cell contact is essential for appropriate co-ordination of development and it initiates significant signalling events. During myogenesis, committed myoblasts migrate to sites of muscle formation, align and form adhesive contacts that instigate cell-cycle exit and terminal differentiation into multinucleated myotubes; thus myogenesis is an excellent paradigm for the investigation of signals derived from cell-cell contact. PI3-K and p38 MAPK are both essential for successful myogenesis. Pro-myogenic growth factors such as IGF-II activate PI3-K via receptor tyrosine kinases but the extracellular cues and upstream intermediates required for activation of the p38 MAPK pathway in myoblast differentiation are not known. Initial observations suggested a correlation between p38 MAPK phosphorylation and cell density, which was also related to N-cadherin levels and Igf2 expression. Subsequent studies using N-cadherin ligand, dominant-negative N-cadherin, constitutively active and dominant-negative forms of RhoA, and MKK6 and p38 constructs, reveal a novel pathway in differentiating myoblasts that links cell-cell adhesion via N-cadherin to Igf2 expression (assessed using northern and promoter-reporter analyses) via RhoA and p38α and/or β but not γ. We thus define a regulatory mechanism for p38 activation that relates cell-cell-derived adhesion signalling to the synthesis of the major fetal growth factor, IGF-II.

Original languageEnglish
Pages (from-to)4828-4840
Number of pages13
JournalJournal of Cell Science
Issue number23
Publication statusPublished - 1 Dec 2006


  • Cadherin
  • Cell-cell contact
  • IGF-II
  • Myogenic differentiation
  • p38 MAPK
  • RhoA

ASJC Scopus subject areas

  • Cell Biology


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