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Identification and characterization of Runx2 phosphorylation sites involved in matrix metalloproteinase-13 promoter activation |
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| Authors: | Nagarajan Selvamurugan Minnkyong Lee Hong Li |
| Institution: | a Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India b Department of Physiology and Biophysics, UMDNJ - Robert Wood Johnson Medical School, 683 Hoes Lane, Piscataway, NJ 08854, USA c Center for Advanced Proteomics Research, UMDNJ - New Jersey Medical School Cancer Center, Newark, NJ 07103, USA |
| Abstract: | 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. |
| Keywords: | PTH parathyroid hormone PKA protein kinase A 8-Br-cAMP 8-bromo cyclic adenosine mono phosphate MMP-13 matrix metalloproteinase-13 MALDI matrix-assisted laser desorption/ionization TLC thin layer chromatography CAT chloramphenicol acetyl transferase GAPDH glyceraldehyde 3-phosphate dehydrogenase |
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