Recombinant Human CLF-1/CLC Complex Protein

Cardiotrophin-like cytokine (CLC), also known as novel neurotrophin-1 (NNT-1) and B cell stimulating factor (BSF-3), is a member of the IL-6 family of cytokines (1, 2). CLC associates with the secreted soluble cytokine-like factor1 (CLF-1), a member of the Cytokine Type I Receptor family, to form the heteromeric composite cytokine CLC/CLF-1 (3, 5). CLC can also form an alternate composite cytokine with soluble ciliary neurotrophic factor receptor alpha (CNTF R alpha) (4). Co-expression of CLC with either CLF-1 or CNTF R alpha is required for the formation of the composite cytokines and for CLC secretion (3 - 5). CLC/CLF-1 binds to the membrane-associated CNTF R alpha to initiate the heterodimerization between gp130 and leukemia inhibitory factor receptor (LIFR) and stimulate thePI 3-kinase and the MAP kinase activity. The CLC/CLF-1 complex displays activities only on those cells expressing the functional tripartite receptor complex (5). Human and mouse CLF-1 share 96% amino acid sequence identity (3). Human CLC is most homologous to cardiotrophin-1, sharing approximately 29% amino acid sequence homology. Human CLC also shares 96% amino acid sequence homology with mouse CLC. CLC/CLF-1 supports the survival of embryonic motor and sympathetic neurons and has been shown to induce astrocytes differentiation of fetal neuroepithelial cells (4 - 6). Both CLF-1 and CLC are expressed in the embryo, suggesting that the composite cytokine may have an important role in nervous system development (5, 7). CLC has also been shown to regulate immune functions by stimulating B cell proliferation and Ig production (8).