Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family.
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/BSF-3 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/BSF-3 is a gp130 activator with B-cell stimulating capability.
Senaldi
G
G
Amgen Inc., Thousand Oaks, CA 91320, USA. gsnaldi@amgen.com
Varnum
B C
BC
Sarmiento
U
U
Starnes
C
C
Lile
J
J
Scully
S
S
Guo
J
J
Elliott
G
G
McNinch
J
J
Shaklee
C L
CL
Freeman
D
D
Manu
F
F
Simonet
W S
WS
Boone
T
T
Chang
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D003345:Corticosterone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000096:biosynthesis
D001053:Apolipoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D003345:Corticosterone