Identification and characterization of Runx2 phosphorylation sites involved in matrix metalloproteinase-13 promoter activation

Nagarajan Selvamurugan, Emi Shimizu, Minnkyong Lee, Tong Liu, Hong Li, Nicola C. Partridge

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1141-1146
Number of pages6
JournalFEBS Letters
Volume583
Issue number7
DOIs
StatePublished - Apr 2 2009

Keywords

  • Collagenase-3
  • Cyclic adenosine mono phosphate
  • Matrix metalloproteinase-13
  • Parathyroid hormone
  • Runx2

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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