TY - JOUR
T1 - Identification and characterization of Runx2 phosphorylation sites involved in matrix metalloproteinase-13 promoter activation
AU - Selvamurugan, Nagarajan
AU - Shimizu, Emi
AU - Lee, Minnkyong
AU - Liu, Tong
AU - Li, Hong
AU - Partridge, Nicola C.
N1 - Funding Information:
We thank Dr. Gerard Karsenty for providing the rat Runx2 (type II) construct. This work was supported by a research grant (DK 47420) from the National Institutes of Health (to N.C.P.).
PY - 2009/4/2
Y1 - 2009/4/2
N2 - Matrix metalloproteinase-13 (MMP-13) plays a critical role in parathyroid hormone (PTH)-induced bone resorption. PTH acts via protein kinase A (PKA) to phosphorylate and stimulate the transactivation of Runx2 for MMP-13 promoter activation. We show here that PTH stimulated Runx2 phosphorylation in rat osteoblastic cells. Runx2 was phosphorylated on serine 28 and threonine 340 after 8-bromo cyclic adenosine mono phosphate (8-Br-cAMP) treatment. We further demonstrate that in the presence of 8-Br-cAMP, the wild-type Runx2 construct stimulated MMP-13 promoter activity, while the Runx2 construct having mutations at three phosphorylation sites (S28, S347 and T340) was unable to stimulate MMP-13 promoter activity. Thus, we have identified the Runx2 phosphorylation sites necessary for PKA stimulated MMP-13 promoter activation and this event may be critical for bone remodeling.
AB - Matrix metalloproteinase-13 (MMP-13) plays a critical role in parathyroid hormone (PTH)-induced bone resorption. PTH acts via protein kinase A (PKA) to phosphorylate and stimulate the transactivation of Runx2 for MMP-13 promoter activation. We show here that PTH stimulated Runx2 phosphorylation in rat osteoblastic cells. Runx2 was phosphorylated on serine 28 and threonine 340 after 8-bromo cyclic adenosine mono phosphate (8-Br-cAMP) treatment. We further demonstrate that in the presence of 8-Br-cAMP, the wild-type Runx2 construct stimulated MMP-13 promoter activity, while the Runx2 construct having mutations at three phosphorylation sites (S28, S347 and T340) was unable to stimulate MMP-13 promoter activity. Thus, we have identified the Runx2 phosphorylation sites necessary for PKA stimulated MMP-13 promoter activation and this event may be critical for bone remodeling.
KW - Collagenase-3
KW - Cyclic adenosine mono phosphate
KW - Matrix metalloproteinase-13
KW - Parathyroid hormone
KW - Runx2
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U2 - 10.1016/j.febslet.2009.02.040
DO - 10.1016/j.febslet.2009.02.040
M3 - Article
C2 - 19264160
AN - SCOPUS:62849108358
VL - 583
SP - 1141
EP - 1146
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 7
ER -