Extracellular heat shock protein HSP90β secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-β1

Shigeki Suzuki, Ashok B. Kulkarni

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Transforming growth factor-beta 1 (TGF-β1) is secreted as a latent complex, which consists of latency-associated peptide (LAP) and the mature ligand. The release of the mature ligand from LAP usually occurs through conformational change of the latent complex and is therefore considered to be the first step in the activation of the TGF-β signaling pathway. So far, factors such as heat, pH changes, and proteolytic cleavage are reportedly involved in this activation process, but the precise molecular mechanism is still far from clear. Identification and characterization of the cell surface proteins that bind to LAP are important to our understanding of the latent TGF-β activation process. In this study, we have identified heat shock protein 90 β (HSP90β) from the cell surface of the MG63 osteosarcoma cell line as a LAP binding protein. We have also found that MG63 cells secrete HSP90β into extracellular space which inhibits the activation of latent TGF-β1, and that there is a subsequent decrease in cell proliferation. TGF-β1-mediated stimulation of MG63 cells resulted in the increased cell surface expression of HSP90β. Thus, extracellular HSP90β is a negative regulator for the activation of latent TGF-β1 modulating TGF-β signaling in the extracellular domain.

Original languageEnglish
Pages (from-to)525-531
Number of pages7
JournalBiochemical and biophysical research communications
Volume398
Issue number3
DOIs
Publication statusPublished - 2010 Jul
Externally publishedYes

Keywords

  • Extracellular HSP90β
  • Latent TGF-β activation
  • MG63 cell
  • Osteosarcoma
  • TGF-β1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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