title: Dentin matrix protein 1 (DMP1) signals via cell surface integrin.
abstract: Dentin matrix phosphoprotein 1 (DMP1) is a non-collagenous, acidic extracellular matrix protein expressed chiefly in bone and dentin. We examined the DMP1 ability to engage cell-surface receptors and subsequently activate intracellular signaling pathways. Our data indeed show that the presence of extracellular DMP1 triggers focal adhesion point formation in human mesenchymal stem cells and osteoblast-like cells. We determine that DMP1 acts via interaction with αvβ3 integrin and stimulates phosphorylation of focal adhesion kinase. Further biochemical characterization confirms the activation of downstream effectors of the MAPK pathways, namely ERK and JNK, after DMP1 treatment. This activation is specifically inhibitable and can also be blocked by the addition of anti-αvβ3 integrin antibody. Furthermore, we show that extracellular treatment with DMP1 stimulates the translocation of phosphorylated JNK to the nucleus and a concomitant up-regulation of transcriptional activation by phosphorylated c-Jun. The evidence presented here indicates that DMP1 is specifically involved in signaling via extracellular matrix-cell surface interaction. Combined with the published DMP1-null data (Feng, J. Q., Ward, L. M., Liu, S., Lu, Y., Xie, Y., Yuan, B., Yu, X., Rauch, F., Davis, S. I., Zhang, S., Rios, H., Drezner, M. K., Quarles, L. D., Bonewald, L. F., and White, K. E. (2006) Nat. Genet. 38, 1310-1315) it can be hypothesized that DMP1 could be a key effector of ECM-osteocyte signaling.
authors.affiliation: Department of Stomotology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Pang-Ning
authors.initials: PN
authors.lastname: Teng
authors.forename: Thottala
authors.initials: T
authors.lastname: Jayaraman
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Onishi
authors.forename: Jinhua
authors.initials: J
authors.lastname: Li
authors.forename: Leslie
authors.initials: L
authors.lastname: Bannon
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Huang
authors.forename: John
authors.initials: J
authors.lastname: Close
authors.forename: Charles
authors.initials: C
authors.lastname: Sfeir
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; D039302:Integrin alphaVbeta3; D010750:Phosphoproteins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4