Identification of residues in the putative 5th helical region of human interleukin‐6, important for activation of the IL‐6 signal transducer, gp130

FEBS Letters

Grötzinger, Joachim³  Brakenhoff, Just P.J¹  Aarden, Lucien A¹  Rose-John, Stefan²  Klaasse Bos, Hanny¹ 

[1] Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands;I. Medical Clinic, Section Pathophysiology, Mainz University, D-55101 Mainz, Germany;Department of Biochemistry, RWTH Aachen, D-52057 Aachen, Germany

关键词: Interleukin-6;    Structure-function analysis;    gp130;    wtIL-6;    wild type interleukin-6;   

DOI  :  10.1016/0014-5793(96)00974-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have previously shown that L58 in the putative 5th helical region of human interleukin-6 (IL-6) is important for activation of the IL-6 signal transducer gp130 [de Hon et al. (1995) FEBS Lett. 369, 187–191]. To further explore the importance of individual residues in this region for gp130 activation we have now combined Ala substitutions of residues E52, S53, S54, K55, E56, L58 and E60 with other substitutions in IL-6, known to affect gp130 activation (Q160E and T163P). The combination mutant protein with L58A completely lost the capacity to induce the proliferation of XG-1 myeloma cells, and could effectively antagonize wild type IL-6 activity on these cells. Moreover, the data suggest that besides L58, S54 particularly, but also E52, S53, K55 and E56 contribute to gp130 activation.

【 授权许可】

Unknown