DPP Activates Integrin-Mediated Anchorage-Dependent Signals in undifferentiated mesenchymal cells
journal contributionposted on 01.11.2013 by Asha Eapen, Amsaveni Ramachandran, Anne George
Any type of content formally published in an academic journal, usually following a peer-review process.
DPP, a major noncollagenous protein of the dentin matrix is a highly acidic protein and binds Ca2+ avidly and thus linked to matrix mineralization. Here, we demonstrate that the RGD domain in DPP can bind to integrins on the cell surface of undifferentiated mesenchymal stem cells and pulp cells. This coupling generates intracellular signals that are channeled along cytoskeletal filaments and activates the nonreceptor tyrosine kinase FAK, which plays a key role in signaling at sites of cellular adhesion. The putative FAK autophosphorylation site Tyr397 is phosphorylated during focal adhesion assembly induced by DPP on the substrate. We further demonstrate that these intracellular signals propagate through the cytoplasm and activate anchorage-dependent ERK signaling. Activated ERK, translocates to the nucleus and phosphorylates the transcription factor ELK-1which in turn coordinate the expression of downstream target genes such as DMP1 and DSP. These studies suggest a novel paradigm which demonstrates that extracellular DPP can induce intracellular signaling which can be propagated to the nucleus and thus alter gene activities.