Yamanaka Y, Nakajima K, Fukada T, Hibi M, Hirano T
Department of Molecular Oncology, Osaka University Medical School, Japan.
EMBO J. 1996 Apr 1;15(7):1557-65.
Interleukin-6 (IL-6) induces growth arrest and macrophage differentiation through its receptor in a murine myeloid leukaemic cell line, M1, although it is largely unknown how the IL-6 receptor generates these signals. By using chimeric receptors consisting of the extracellular domain of growth hormone receptor and the transmembrane and cytoplasmic domain of gp130 with progressive C-terminal truncations, we showed that the membrane-proximal 133, but not 108, amino acids of gp130 could generate the signals for growth arrest, macrophage differentiation, down-regulation of c-myc and c-myb, induction of junB and IRF1 and Stat3 activation. Mutational analysis of this region showed that the tyrosine residue with the YXXQ motif was critical not only for Stat3 activation but also for growth arrest and differentiation, accompanied by down-regulation of c-myc and c-myb and immediate early induction of junB and IRF1. The tight correlation between Stat3 activation and other IL-6 functions was further observed in the context of the full-length cytoplasmic region of gp130. The result suggest that Stat3 plays an essential role in the signals for growth arrest and differentiation.
白细胞介素-6（IL-6）通过其受体在小鼠髓样白血病细胞系M1中诱导生长停滞和巨噬细胞分化，尽管IL-6受体如何产生这些信号在很大程度上尚不清楚。通过使用由生长激素受体的胞外结构域与gp130的跨膜和胞质结构域组成的嵌合受体，并进行渐进性C末端截短，我们发现gp130膜近端的133个氨基酸而非108个氨基酸能够产生生长停滞、巨噬细胞分化、c-myc和c-myb下调、junB和IRF1诱导以及Stat3激活的信号。对该区域的突变分析表明，具有YXXQ基序的酪氨酸残基不仅对Stat3激活至关重要，而且对生长停滞和分化也至关重要，同时伴随着c-myc和c-myb的下调以及junB和IRF1的立即早期诱导。在gp130全长胞质区域的背景下，进一步观察到Stat3激活与其他IL-6功能之间的紧密相关性。结果表明，Stat3在生长停滞和分化信号中起重要作用。
