CONSTRUCTION AND FUNCTIONAL-ANALYSIS OF HYBRID INTERLEUKIN-6 VARIANTS - CHARACTERIZATION OF THE ROLE OF THE C-TERMINUS FOR SPECIES SPECIFICITY

被引:14
作者
LEEBEEK, FWG [1 ]
FOWLKES, DM [1 ]
机构
[1] UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514
关键词
INTERLEUKIN-6; RECEPTOR; HYBRID PROTEIN; SPECIES SPECIFICITY; GROWTH FACTOR;
D O I
10.1016/0014-5793(92)81013-C
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have constructed several hybrid human interleukin-6 (IL-6) variants in which the carboxyl-terminus, which includes a receptor binding site of IL-6 has been replaced with the C-terminus of various proteins homologous to human IL-6. IL-6 hybrids with the C-terminus of human growth hormone and human granulocyte-colony stimulating factor maintain part of the biological activity of human IL-6. Replacing the C-terminus of human IL-6 with the C-terminus of mouse and rat IL-6 resulted in a normal or increased activity on a mouse cell line; however, this gave a low (to 200-fold less) activity on a human cell line compared to wild-type human IL-6. We therefore conclude that the C-terminus of IL-6 plays an important role in the species specificity of IL-6.
引用
收藏
页码:262 / 264
页数:3
相关论文
共 17 条
  • [1] HEMATOPOIETIC RECEPTORS AND HELICAL CYTOKINES
    BAZAN, JF
    [J]. IMMUNOLOGY TODAY, 1990, 11 (10): : 350 - 354
  • [2] BRAKENHOFF JPJ, 1990, J IMMUNOL, V145, P561
  • [3] BRAKENHOFF JPJ, 1990, THESIS AMSTERDAM, P84
  • [4] HIGH-RESOLUTION EPITOPE MAPPING OF HGH-RECEPTOR INTERACTIONS BY ALANINE-SCANNING MUTAGENESIS
    CUNNINGHAM, BC
    WELLS, JA
    [J]. SCIENCE, 1989, 244 (4908) : 1081 - 1085
  • [5] INTERNAL DELETIONS IN HUMAN INTERLEUKIN-6 - STRUCTURE-FUNCTION ANALYSIS
    FONTAINE, V
    BRAKENHOFF, J
    DEWIT, L
    ARCONE, R
    CILIBERTO, G
    CONTENT, J
    [J]. GENE, 1991, 104 (02) : 227 - 234
  • [6] JAMBOU RC, 1988, P NATL ACAD SCI USA, V139, P4116
  • [7] THE BIOLOGY OF INTERLEUKIN-6
    KISHIMOTO, T
    [J]. BLOOD, 1989, 74 (01) : 1 - 10
  • [8] LEEBEEK FWG, 1992, IN PRESS J BIOL CHEM
  • [9] NORTHEMANN W, 1989, J BIOL CHEM, V264, P16072
  • [10] PRIMER-DIRECTED ENZYMATIC AMPLIFICATION OF DNA WITH A THERMOSTABLE DNA-POLYMERASE
    SAIKI, RK
    GELFAND, DH
    STOFFEL, S
    SCHARF, SJ
    HIGUCHI, R
    HORN, GT
    MULLIS, KB
    ERLICH, HA
    [J]. SCIENCE, 1988, 239 (4839) : 487 - 491