Effect of IGFBP-3 on IGF- and IGF-analogue-induced insulin-like growth factor-I receptor (IGFIR) signalling

Gayathri R. Devi, Donna L. Graham, Youngman Oh, Ronald (Ron) Rosenfeld

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Abstract

Insulin-like growth factor binding protein-3 (IGFBP-3) binds IGF-I and IGF-II with high affinity, at least an order of magnitude higher than the affiniy of the IGFs for the IGFIR. It has been hypothesized that IGFBP-3 inhibits IGF binding to the IGFIR via a mechanism independent of its ability to sequester IGFs. In the present study, we examined the effects of IGFBP-3 and its proteolytic fragments on the initial events of the IGFIR signalling pathway. IGFBP-3 inhibited IGF-I-, IGF-II-, Des(1-3)IGF-I- and Long(R3)IGF-I-induced IGFIR phosphorylation in a dose-dependent manner at similar concentration range but not QAYL-induced IGFIR-P. The (1-97)IGFBP-3 fragment was able to inhibit only IGF-I-induced IGFIR-P. The (1-97)IGFBP-3 fragment but not intact IGFBP-3 inhibited insulin-induced IGFIR-P. Monolayer cross-linking with [ 125I]IGFBP-3 indicated that there is no direct interaction of IGFBP-3 with the IGFIR. This study demonstrates that the effect on the initial step of IGFIR signalling by IGFBP-3 is largely due to its ability to sequester IGF and the IGF analogues in the extracellular milieu and not the result of any interaction of IGFBP-3 with the IGFIR or a mechanism independent of its ability to bind IGFs.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalGrowth Hormone and IGF Research
Volume11
Issue number4
DOIs
Publication statusPublished - 2001

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Keywords

  • Des-IGF-I
  • IGF-I receptor signalling
  • IGFBP-3
  • IGFBP-3 proteolysis
  • Long-R3-IGF-I

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of IGFBP-3 on IGF- and IGF-analogue-induced insulin-like growth factor-I receptor (IGFIR) signalling. / Devi, Gayathri R.; Graham, Donna L.; Oh, Youngman; Rosenfeld, Ronald (Ron).

In: Growth Hormone and IGF Research, Vol. 11, No. 4, 2001, p. 231-239.

Research output: Contribution to journalArticle