Effect of IGFBP-derived peptides on incorporation of (SO4)-S-35 into proteoglycans

18 amino acid peptides from the G-terminal region of IGFBP-3, -5 (P3, P5), increased the incorporation of (SO4)-S-35 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 amin o acids changed to the basic amino acid in the equivalent position of P3. T he 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 s crambled version of P3 was less effective than P3. P3, P5, P6, P3F and all P6 variants all stimulated glucose uptake, which occurred only in microvess el cells. P1, P2, P4, and equimolar intact IGFBP-3 stimulated neither gluco se uptake nor sulfate incorporation. Thus, C-terminal basic portions of IGF BP-3, -5 and -6 alter two specific functions of endothelial cells with suff icient differences to suggest mediation by distinct mechanisms. (C) 2000 Ha rcourt Publishers Ltd.