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DPP Activates Integrin-Mediated Anchorage-Dependent Signals in undifferentiated mesenchymal cells

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Title: DPP Activates Integrin-Mediated Anchorage-Dependent Signals in undifferentiated mesenchymal cells
Author(s): Eapen, Asha; Ramachandran, Amsaveni; George, Anne
Subject(s): DPP Integrins FAK Extracellular matrix Differentiation Gene expression Dentin
Abstract: 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.
Issue Date: 2012-02-17
Publisher: American Society for Biochemistry and Molecular Biology
Citation Info: Eapen, A. S., Ramachandran, A., & George, A. 2011. Dentin phosphoprotein (DPP) activates integrin-mediated anchorage-dependent signals in undifferentiated mesenchymal cells. Journal of Biological Chemistry, 287(8): 5211-24. doi: 10.1074/jbc.M111.290080
Type: Article
Description: This research was originally published in Journal of Biological Chemistry. Eapen A, Ramachandran A, George A.. Dentin phosphoprotein (DPP) activates integrin-mediated anchorage-dependent signals in undifferentiated mesenchymal cells. Journal of Biological Chemistry. 2012. 287(8):5211-24. © the American Society for Biochemistry and Molecular Biology.
URI: http://hdl.handle.net/10027/10395
ISSN: 0021-9258
Sponsor: This work was supported by National Institutes of Health Grant DE 19633 and the Brodie Endowment Fund.
Date Available in INDIGO: 2013-11-01
 

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