Parathyroid hormone signaling through low-density lipoprotein-related protein 6

Creative Commons License

Wan M., Yang C., Li J., Wu X., Yuan H., Ma H., ...Daha Fazla

GENES & DEVELOPMENT, cilt.22, sa.21, ss.2968-2979, 2008 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 21
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1101/gad.1702708
  • Dergi Adı: GENES & DEVELOPMENT
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.2968-2979
  • Anahtar Kelimeler: PTH signaling, LRP6, osteoblasts, beta-catenin, PKA
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

Intermittent administration of PTH stimulates bone formation, but the precise mechanisms responsible for PTH responses in osteoblasts are only incompletely understood. Here we show that binding of PTH to its receptor PTH1R induced association of LRP6, a coreceptor of Wnt, with PTH1R. The formation of the ternary complex containing PTH, PTH1R, and LRP6 promoted rapid phosphorylation of LRP6, which resulted in the recruitment of axin to LRP6, and stabilization of beta-catenin. Activation of PKA is essential for PTH-induced beta-catenin stabilization, but not for Wnt signaling. In vivo studies confirmed that PTH treatment led to phosphorylation of LRP6 and an increase in amount of beta-catenin in osteoblasts with a concurrent increase in bone formation in rat. Thus, LRP6 coreceptor is a key element of the PTH signaling that regulates osteoblast activity.