Article

CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex

Centre d'Immunologie Pierre Fabre, 5 Avenue Napoleon III, 74164 St. Julien-en-Genevois, France.
Nature Neuroscience (Impact Factor: 14.98). 10/2000; 3(9):867-72. DOI: 10.1038/78765
Source: PubMed

ABSTRACT Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, CNTFR, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second, developmentally important ligand. We have identified this factor as a stable secreted complex of cardiotrophin-like cytokine (CLC) and the soluble receptor cytokine-like factor-1 (CLF). CLF expression was required for CLC secretion, and the complex acted only on cells expressing functional CNTF receptors. The CLF/CLC complex activated gp130, LIFR and signal transducer and activator of transcription 3 (STAT3) and supported motor neuron survival. Our results indicate that the CLF/CLC complex is a second ligand for CNTFR with potentially important implications in nervous system development.

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    • "The CRLF1 protein is a member of the ciliary neurotrophic factor receptor (CNTFR; MIM #118946; locus 9p13.3) pathway and interacts with cardiotrophin-like cytokine factor 1 (CLCF1; MIM #607672; locus 11q13.2) to form a stable heterodimeric complex, CRLF1/CLCF1, which belongs to the family of the interleukin-6 (IL-6) cytokine family and acts as a second functional ligand for the CNTF receptor alpha [Elson et al., 2000], composed by gp130 (MIM #600694; locus 5q11.2) and leukemia inhibitory factor receptor beta (LIFR; MIM# 151443; locus 5p13.1). This pathway is known to be important for the development and maintenance of the nervous system and muscles. "
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    • "cytokine-like factor (CLF). The heterodimer conformation of CLC/CLF is found to be similar to that of IL-12, although both subunits are not linked via a disulphide bridge [8]. The CLC/CLF dimers signal via the CNTF receptor complex. "
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    Current Medicinal Chemistry 11/2012; 20(2). DOI:10.2174/0929867311320020005 · 3.85 Impact Factor
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    • "Interestingly, CT-1 is secreted from newly generated neurons, suggesting that astrogliogenesis is triggered in part by the accumulation of CT-1-expressing neurons. Other gp130 family cytokines including NP and the cardiotrophin-like cytokine (CLC; also known as novel neurotrophin 1 and B cell stimulating factor 3), which binds CNTFRa together with cytokine-like factor 1 (CLF1) (Elson et al., 2000), could also have a role in gliogenesis since the gliogenesis phenotype in the CT-1 mice is apparently not as severe as that seen in gp130 or LIFRb KO mice. "
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