Structure-function relationships in the heparin-binding C-terminal region of insulin-like growth factor binding protein-3.
IGFBP-3 contains a carboxyterminal basic region which, when present as an isolated 18 amino acid peptide (P3), binds heparin, associates with cultured endothelial cells and stimulates glucose uptake. The P3 molecule has now been modified relative to charge, amino acid sequence and size to determine structure-function relationships relative to four properties of P3: affinity for heparin; inhibition of IGFBP-3 binding; stimulation of glucose uptake; and displacement of bFGF from the extracellular matrix of endothelial cells. Results indicate: (1) the presence or absence of heparin binding was concordant with the presence/absence of the other three properties; (2) the number of basic amino acids was an important, if not limiting, factor for each property; (3) the order of potency of the basic amino acids was arginine = lysine > > histidine; (4) the unrelated, basic protein, protamine, mimics all properties of P3; and (5) the putative consensus heparin-binding sequence of P3 was not essential for any of the P3 activities.
Booth
B A
BA
Veterans Administration Medical Center, Department of Internal Medicine, Iowa City, Iowa 52246, USA.
Boes
M
M
Dake
B L
BL
Linhardt
R J
RJ
Caldwell
E E
EE
Weiler
J M
JM
Bar
R S
RS
D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000378:metabolism*; D000963:Antimetabolites / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D000963:Antimetabolites; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D006493:Heparin; D003847:Deoxyglucose