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TGF-beta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling.

ABSTRACT: Parathyroid hormone (PTH) regulates calcium homeostasis and bone metabolism by activating PTH type I receptor (PTH1R). Here we show that transforming growth factor (TGF)-beta type II receptor (TbetaRII) forms an endocytic complex with PTH1R in response to PTH and regulates signalling by PTH and TGF-beta. TbetaRII directly phosphorylates the PTH1R cytoplasmic domain, which modulates PTH-induced endocytosis of the PTH1R-TbetaRII complex. Deletion of TbetaRII in osteoblasts increases the cell-surface expression of PTH1R and augments PTH signalling. Conditional knockout of TbetaRII in osteoblasts in mice results in a high bone mass with increased trabecular bone and decreased cortical bone, similar to the bone phenotype in mice expressing a constitutively active PTH1R. Disruption of PTH signalling by injection of PTH(7-34) or ablation of PTH1R rescues the bone phenotype of TbetaRII knockout mice. These studies reveal a previously unrecognized function for TbetaRII and a mechanism for integration of PTH and local growth factor at the membrane receptor level.

SUBMITTER: Qiu T

PROVIDER: S-EPMC3704184 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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TGF-beta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling.

Qiu Tao T Wu Xiangwei X Zhang Fengjie F Clemens Thomas L TL Wan Mei M Cao Xu X

Nature cell biology 20100207 3

Parathyroid hormone (PTH) regulates calcium homeostasis and bone metabolism by activating PTH type I receptor (PTH1R). Here we show that transforming growth factor (TGF)-beta type II receptor (TbetaRII) forms an endocytic complex with PTH1R in response to PTH and regulates signalling by PTH and TGF-beta. TbetaRII directly phosphorylates the PTH1R cytoplasmic domain, which modulates PTH-induced endocytosis of the PTH1R-TbetaRII complex. Deletion of TbetaRII in osteoblasts increases the cell-surfa ...[more]

PMID: 20139972

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TGF-beta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling.

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TGF-beta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling.

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