Publications [#99273] of Gayathri R Devi

Papers Published

1. GR Devi, DL Graham, Y Oh, RG Rosenfeld, Effect of IGFBP-3 on IGF- and IGF-analogue-induced insulin-like growth factor-I receptor (IGFIR) signalling., Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, vol. 11 no. 4 (August, 2001), pp. 231-9, ISSN 1096-6374 [doi]
   (last updated on 2013/05/16)

   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 [(125)I]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.

   Keywords:
   3T3 Cells • Animals • Binding, Competitive • Cross-Linking Reagents • Dose-Response Relationship, Drug • Humans • Insulin • Insulin-Like Growth Factor Binding Protein 2 • Insulin-Like Growth Factor Binding Protein 3 • Insulin-Like Growth Factor I • Insulin-Like Growth Factor II • Ligands • Mice • Phosphorylation • Precipitin Tests • Protein Binding • Receptor, IGF Type 1 • Signal Transduction* • analogs & derivatives • biosynthesis • metabolism • metabolism* • pharmacology • pharmacology*