Structure-function relationships of insulin-like growth factor binding protein 6 (IGFBP-6) and its chimeras

Growth Horm IGF Res. 2002 Apr;12(2):91-8. doi: 10.1054/ghir.2001.0266.

Abstract

Insulin-like growth factor binding protein 6 (IGFBP-6) is a high-affinity IGFBP with substantially greater affinity for insulin-like growth factor-II (IGF-II) than IGF-I. IGFBP-6(3) is a chimera which has a 20 amino acidC -terminal portion of IGFBP-6 switched with the homologous area of IGFBP-3, P3. Unlike IGFBP-4(3), in which the P3 region was exchanged for the homologous region of IGFBP-4 (P4), IGFBP-6(3) does not bind to endothelial cells. Double mutations were made with the P3 region exchanged as well as a second area differing from IGFBP-3 to form IGFBP-6(3)A and IGFBP-6(3)B, by replacing this area with the homologous region of IGFBP-3. Neither [(125)I]IGFBP-6(3)A nor IGFBP-6(3)B specifically bound to endothelial cells. However, each double mutant competed for [(125)I]IGFBP-3 binding to cultured cells. In the perfused heart, transendothelial transport of IGFBP-6 and IGFBP-6(3) was only 25% of similar transendothelial transport of perfused IGFBP-3. We conclude that chimeras of IGFBP-6 and IGFBP-3(6) clearly differ from IGFBP-4(3) in their ability to bind specifically to endothelial cells and in their capacity to undergo transendothelial transportation in the perfused heart.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelium / cytology
  • Endothelium, Vascular / cytology
  • Heart / physiology
  • Insulin-Like Growth Factor Binding Protein 4 / chemistry*
  • Insulin-Like Growth Factor Binding Protein 4 / metabolism
  • Insulin-Like Growth Factor Binding Protein 6 / chemistry*
  • Insulin-Like Growth Factor Binding Protein 6 / physiology*
  • Insulin-Like Growth Factor II / metabolism
  • Ligands
  • Molecular Sequence Data
  • Mutation
  • Perfusion
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship

Substances

  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Protein 6
  • Ligands
  • Insulin-Like Growth Factor II