Guo N H, Krutzsch H C, Vogel T, Roberts D D
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1992 Sep 5;267(25):17743-7.
A laminin-binding peptide (peptide G), predicted from the cDNA sequence for a 33-kDa protein related to the 67-kDa laminin receptor, specifically inhibits binding of laminin to heparin and sulfatide. Since the peptide binds directly to heparin and inhibits interaction of another heparin-binding protein with the same sulfated ligands, this inhibition is due to direct competition for binding to sulfated glycoconjugates rather than an indirect effect of interaction with the binding site on laminin for the 67-kDa receptor. Direct binding of laminin to the peptide is also inhibited by heparin. This interaction may result from contamination of the laminin with heparan sulfate, as binding is enhanced by the addition of substoichiometric amounts of heparin but inhibited by excess heparin and two heparin-binding proteins. Furthermore, laminin binds more avidly to a heparin-binding peptide derived from thrombospondin than to the putative receptor peptide. Adhesion of A2058 melanoma cells on immobilized peptide G is also heparin-dependent, whereas adhesion of the cells on laminin is not. Antibodies to the beta 1-integrin chain or laminin block adhesion of the melanoma cells to laminin but not to peptide G. Thus, the reported inhibition of melanoma cell adhesion to endothelial cells by peptide G may result from inhibition of binding of laminin or other proteins to sulfated glycoconjugate receptors rather than from specific inhibition of laminin binding to the 67-kDa receptor.
一种层粘连蛋白结合肽(肽G),由与67 kDa层粘连蛋白受体相关的33 kDa蛋白质的cDNA序列预测而来,可特异性抑制层粘连蛋白与肝素和硫苷脂的结合。由于该肽直接与肝素结合,并抑制另一种肝素结合蛋白与相同硫酸化配体的相互作用,这种抑制是由于对硫酸化糖缀合物结合的直接竞争,而非与67 kDa受体在层粘连蛋白上的结合位点相互作用的间接效应。肝素也会抑制层粘连蛋白与该肽的直接结合。这种相互作用可能是由于层粘连蛋白被硫酸乙酰肝素污染所致,因为亚化学计量的肝素添加会增强结合,但过量肝素和两种肝素结合蛋白会抑制结合。此外,层粘连蛋白与源自血小板反应蛋白的肝素结合肽的结合比与假定的受体肽的结合更紧密。A2058黑色素瘤细胞在固定化肽G上的黏附也是肝素依赖性的,而细胞在层粘连蛋白上的黏附则不是。针对β1整合素链或层粘连蛋白的抗体可阻断黑色素瘤细胞与层粘连蛋白的黏附,但不能阻断与肽G的黏附。因此,报道的肽G对黑色素瘤细胞与内皮细胞黏附的抑制作用可能是由于抑制了层粘连蛋白或其他蛋白质与硫酸化糖缀合物受体的结合,而非特异性抑制层粘连蛋白与67 kDa受体的结合。