Title | Convergence of Igf2 expression and adhesion signalling via RhoA and p38 MAPK enhances myogenic differentiation |
---|
Authors | Lovett, F.A., Gonzalez, I., Salih, D.A.M., Cobb, L.J., Tripathi, G., Cosgrove, R.A., Murrell, A., Kilshaw, P.J. and Pell, J.M. |
---|
Abstract | 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. |
---|
Journal | Journal of Cell Science |
---|
Journal citation | 119, pp. 4828-4840 |
---|
ISSN | 0021-9533 |
---|
Year | 2006 |
---|
Publisher | The Company of Biologists Ltd. |
---|
Digital Object Identifier (DOI) | https://doi.org/10.1242/jcs.03278 |
---|
Publication dates |
---|
Published | 27 Nov 2006 |
---|