title: Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family.
abstract: 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.
authors.affiliation: Amgen Inc., Thousand Oaks, CA 91320, USA. gsnaldi@amgen.com
authors.forename: G
authors.initials: G
authors.lastname: Senaldi
authors.forename: B C
authors.initials: BC
authors.lastname: Varnum
authors.forename: U
authors.initials: U
authors.lastname: Sarmiento
authors.forename: C
authors.initials: C
authors.lastname: Starnes
authors.forename: J
authors.initials: J
authors.lastname: Lile
authors.forename: S
authors.initials: S
authors.lastname: Scully
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: G
authors.initials: G
authors.lastname: Elliott
authors.forename: J
authors.initials: J
authors.lastname: McNinch
authors.forename: C L
authors.initials: CL
authors.lastname: Shaklee
authors.forename: D
authors.initials: D
authors.lastname: Freeman
authors.forename: F
authors.initials: F
authors.lastname: Manu
authors.forename: W S
authors.initials: WS
authors.lastname: Simonet
authors.forename: T
authors.initials: T
authors.lastname: Boone
authors.forename: M S
authors.initials: MS
authors.lastname: Chang
mesh_terms: 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
chemical_list: D001053:Apolipoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D003345:Corticosterone