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Dentin matrix protein 1 (DMP1) signals via cell surface integrin
Hong Wu1, Pang-Ning Teng, Thottala Jayaraman
1Department of Stomotology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
The Journal of Biological Chemistry
|June 7, 2011
Summary
Dentin matrix phosphoprotein 1 (DMP1) activates cell signaling pathways by interacting with cell surface receptors like αvβ3 integrin. This interaction stimulates focal adhesion formation and downstream MAPK signaling, suggesting DMP1
Area of Science:
- Biochemistry
- Cell Biology
- Extracellular Matrix Biology
Background:
- Dentin matrix phosphoprotein 1 (DMP1) is a key non-collagenous protein in bone and dentin.
- Its role in cell signaling and interaction with cell surface receptors is not fully understood.
Purpose of the Study:
- To investigate how extracellular DMP1 engages cell-surface receptors and activates intracellular signaling pathways.
- To elucidate the specific molecular mechanisms underlying DMP1-mediated cell signaling.
Main Methods:
- Cell culture of human mesenchymal stem cells and osteoblast-like cells.
- Treatment with recombinant DMP1 and anti-αvβ3 integrin antibodies.
- Analysis of focal adhesion formation, focal adhesion kinase (FAK) phosphorylation, MAPK pathway activation (ERK, JNK), and c-Jun transcriptional activity.
Main Results:
- Extracellular DMP1 induces focal adhesion formation and FAK phosphorylation in mesenchymal stem cells and osteoblast-like cells.
- DMP1 activates the MAPK pathways, specifically ERK and JNK, which is inhibitable by anti-αvβ3 integrin antibodies.
- DMP1 treatment promotes nuclear translocation of phosphorylated JNK and upregulates phosphorylated c-Jun-mediated transcriptional activity.
Conclusions:
- DMP1 acts as a signaling molecule by interacting with the αvβ3 integrin receptor.
- This interaction initiates intracellular signaling cascades, including MAPK pathway activation, influencing cell behavior.
- DMP1 is implicated as a crucial mediator of extracellular matrix-osteocyte communication.
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