Recombinant Human CLC/CNTFR alpha Chimera Protein

Cardiotrophin-like cytokine (CLC), (also known as novel neurotrophin-1 (NNT-1) and B cell stimulating factor (BSF-3) is a 22 - 25 kDa member of the IL-6 family of cytokines (1 - 3). As such, it is expressed as a long, type I cytokine with four alpha -helices in its structure (2). Human CLC is synthesized as a 225 amino acid (aa) precursor that contains a 27 aa signal sequence and a 198 aa mature region. It contains one potential N-linked glycosylation site that is apparently utilized, and two distinct binding sites for Ciliary Neurotrophic Factor Receptor alpha (CNTF R alpha ) and Cytokine Receptor-like Factor (CLF) (4, 5). Although CLC has a signal sequence, it is not secreted unless noncovalently complexed to either CLF or soluble CNTF R alpha (5, 6). Once complexed, CLC signals through a tripartite receptor complex composed of gp130, LIF R beta and CNTF R alpha (5, 7). Within the IL-6 family, human CLC is most homologous to cardiotrophin-1, sharing approximately 29% amino acid sequence identity (8). Human to mouse, mature CLC shares 96% aa sequence identity. CLC is a trophic factor for motor neurons, a stimulator of ACTH release from corticotrophs, and an inducer of IgE synthesis and B cell proliferation (9 - 11). Cells known to express CLC include embryonic muscle, lung epithelium, and mesenchyme in various regions (12).