Novel neurotrophin-1/B cell-stimulating factor-3: A cytokine of the IL-6 family

被引:198
作者
Senaldi, G [1 ]
Varnum, BC [1 ]
Sarmiento, U [1 ]
Starnes, C [1 ]
Lile, J [1 ]
Scully, S [1 ]
Guo, J [1 ]
Elliott, G [1 ]
McNinch, J [1 ]
Shaklee, CL [1 ]
Freeman, D [1 ]
Manu, F [1 ]
Simonet, WS [1 ]
Boone, T [1 ]
Chang, MS [1 ]
机构
[1] Amgen Inc, Amgen Ctr MS152B, Thousand Oaks, CA 91320 USA
关键词
D O I
10.1073/pnas.96.20.11458
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have identified a cytokine of the IL-6 family and named it novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3). NNT-1/BSF-3 cDNA was cloned from activated Jurkat human T cell lymphoma cells. Its sequence predicts a 225-aa protein with a 27-aa signal peptide, a molecular mass of 22 kDa in mature form, and the highest homology to cardiotrophin-1 and ciliary neurotrophic factor. The gene for NNT-1/BSF-3 is on chromosome 11q13. A murine equivalent to NNT-1/BSF-3 also was identified, which shows 96% homology to human NNT-1/BSF-3. NNT-1/BSF-3 mRNA is found mainly in lymph nodes and spleen. NNT-1/BSF-3 induces tyrosine phosphorylation of glycoprotein 130 (gp130), leukemia inhibitory factor receptor beta, and signal transducer and activator of transcription 3 in the SK-N-MC human neuroblastoma cells. NNT-1/BSF3 shows activities typical of IL-6 family members. In vitro, it supports the survival of chicken embryo motor and sympathetic neurons. In mice, it induces serum amyloid A, potentiates the induction by IL-1 of corticosterone and IL-6, and causes body weight loss and B cell hyperplasia with serum IgG and IgM increase. NNT-1/BSF3 is a gp130 activator with B-cell stimulating capability.
引用
收藏
页码:11458 / 11463
页数:6
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