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Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor

D L Andress1

  • 1Medical Service, Veterans Affairs Medical Center, Seattle 98108, USA.

The American Journal of Physiology
|May 12, 1998
PubMed

Insights

Insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) binds to osteoblasts and activates a 420-kDa membrane protein receptor. This interaction stimulates serine/threonine kinase activity, suggesting a role in IGF-independent signaling.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) interacts with osteoblasts.
  • A 420-kDa membrane protein was previously suggested as a potential IGFBP-5 signaling receptor.
  • IGFBP-5 binding to osteoblasts can be downregulated by IGFBP-5 itself.

Purpose of the Study:

  • To affinity-purify the 420-kDa membrane protein using an IGFBP-5 peptide.
  • To investigate the functional properties of the purified 420-kDa protein.
  • To explore the role of IGFBP-5 in receptor phosphorylation and kinase activation.

Main Methods:

  • Affinity purification of the 420-kDa membrane protein using IGFBP-5-(201-218) peptide.
  • In vitro kinase assays using [32P]ATP to assess autophosphorylation and substrate phosphorylation.
  • Incubation with intact IGFBP-5 and various IGFBP-5 fragments to study phosphorylation enhancement.

Main Results:

  • The 420-kDa membrane protein was successfully purified.
  • The purified protein exhibited autophosphorylation at serine residues.
  • IGFBP-5, IGFBP-5-(1-169), and IGFBP-5-(201-218) enhanced the serine phosphorylation of the 420-kDa protein.
  • The IGFBP-5 receptor phosphorylated casein on serine residues in the presence of [32P]ATP.

Conclusions:

  • IGFBP-5 stimulates the phosphorylation of its putative 420-kDa membrane receptor.
  • The data suggest that serine/threonine kinase activation is involved in mediating IGF-independent effects of IGFBP-5.
  • These findings identify a novel signaling pathway for IGFBP-5 in osteoblasts.

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