Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3)/cardiotrophin-like cytokine (CLC)--a novel gp130 cytokine with pleiotropic functions.

Novel neurotrophin-1/B-cell stimulating factor-3 (NNT-1/BSF-3) is a new member of the gp130 cytokine family. NNT-1/BSF-3 is a second ligand to the tripartite CNTFR complex and activates Jak-STAT, MAPK and PI3/Akt signaling pathways in various cell systems. So far, the known functions of NNT-1/BSF-3 encompass neurotrophic and B cell stimulatory effects, as well as neuroimmunoendocrine modulation of corticotroph function. Gene expression of NNT-1/BSF-3 is stimulated by PKA- and PKC-dependent pathways. Cellular secretion of NNT-1/BSF-3 requires heteromeric complex formation with other factors, e.g. cytokine-like factor-1 (CLF-1) or soluble ciliary neurotrophic factor receptor (sCNTFR). This article reviews the current knowledge on NNT-1/BSF-3 expression, secretion, receptor interaction, signal transduction and physiologic effects of this novel gp130 cytokine. Remark: After preparation of this manuscript, another novel gp130 cytokine named neuropoietin (NP) has been reported and shown to be a ligand of the CNTFR complex.