Effect of IGFBP-derived peptides on incorporation of(35)SO(4)into proteoglycans.
18 amino acid peptides from the C-terminal region of IGFBP-3, -5 (P3, P5), increased the incorporation of(35)SO(4)into proteoglycans in endothelial cells with greater stimulation in large vessel than microvessel cells. The homologous region of IGFBP-6 (P6) also stimulated sulfate uptake, but less potently than P3 and P5. P6 variants were synthesized with one or two amino acids changed to the basic amino acid in the equivalent position of P3. The P6 variants with one additional basic amino acid behaved similarly to P6. The P6 mutant with two altered amino acids was equipotent to P3. P3F, a scrambled version of P3 was less effective than P3. P3, P5, P6, P3F and all P6 variants all stimulated glucose uptake, which occurred only in microvessel cells. P1, P2, P4, and equimolar intact IGFBP-3 stimulated neither glucose uptake nor sulfate incorporation. Thus, C-terminal basic portions of IGFBP-3, -5 and -6 alter two specific functions of endothelial cells with sufficient differences to suggest mediation by distinct mechanisms.
Booth
B A
BA
Diabetes and Endocrinology Research Center, The University of Iowa, Veterans Administration Medical Center, 3E19 VA, Iowa City, IA 52246, USA.
Boes
M
M
Dake
B L
BL
Caldwell
E E
EE
Weiler
J M
JM
Bar
R S
RS
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D010446:Peptide Fragments; D011509:Proteoglycans; D013431:Sulfates