Structure-function relationships of insulin-like growth factor binding protein 6 (IGFBP-6) and its chimeras.
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.
Boes
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M
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, IA 52246, USA.
Dake
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Booth
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Sandra
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Bateman
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Knudtson
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D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D006321:Heart / Q000502:physiology; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000737:chemistry* / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000737:chemistry* / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D010477:Perfusion; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D018974:Insulin-Like Growth Factor Binding Protein 4; D018976:Insulin-Like Growth Factor Binding Protein 6; D008024:Ligands; D007335:Insulin-Like Growth Factor II