Human Multiple Myeloma 세포주 U266에서 IL-6에 의한 Grb2 결합 단백질들의 인산화 = Tyrosine Phosphorylation of Grb2 Associated Proteins in Human Multiple Myeloma Cell Line U266 Stimulated with IL-6

다국어 초록 (Multilingual Abstract)

Interleukin-6 (IL-6) is a pleiotropic cytokine generating multifunctional signals to several cell lines such as B cells, T cells, hepatocytes, myeloma, and leukemic cell lines. To understand the diverse signals generated by IL-6, it is essential to clarify the molecular and cellular events following IL-6 stimulation. IL-6 binding to its receptor triggers the association of the cytoplasmic domain of the receptor (gp80) with a signal transducing unit of IL-6R, gpl3O. Since neither gp80 nor gp130 have any protein tyrosine kinase domain, unknown protein kinases except Janus kinase might be involved in the early steps of IL-6 signal transduction. Like many other cytokines and growth factors, IL-6 activates p2l'az. However the precise biochemical mechanism leading to the p21' activation is still unclear.
It was recently elucidated that she (src homology and collagen) known to activate p21' affected on IL-6 signal pathway. Therefore we investigated the effects of IL-6 on Grb2 (growth factor receptor bound protein 2), which is an element of the Ras pathway in multiple systems. In multiple myeloma cell line U266, IL-6 induced the tyrosine phosphorylation of several Grb2-associated proteins 80, 66, 52 and 44kD in a time-dependent manner.
We also observed several protein kinases or substrates, including 44 and 25kD protein, by in vitro kinase assay. These findings suggest that IL-6 might activate the Ras signalling pathway via tyrosine phosphorylation of several Grb2-associated proteins.
Futher studies will be need to elucidate which of the IL-6 receptor-associated cytoplasmic tyrosine kinases or adaptor proteins mediate IL-6 signalling pathway.