CYTOKINE-LIKE FACTOR-I, A NOVEL SOLUBLE-PROTEIN, SHARES HOMOLOGY WITHMEMBERS OF THE CYTOKINE TYPE-I RECEPTOR FAMILY

In this report we describe the identification, cloning, and expression pattern of human cytokine-like factor 1 (hCLF-1) and the identificati on and cloning of its murine homologue, They were identified from expr essed sequence tags using amino acid sequences from conserved regions of the cytokine type I receptor family. Human CLF-1 and murine CLF-1 s hared 96% amino acid identity and significant homology with many cytok ine type I receptors, CLF-1 is a secreted protein, suggesting that it is either a soluble subunit within a cytokine receptor complex, like t he soluble form of the IL-6R alpha-chain, or a subunit of a multimeric ;cytokine, e.g., IL-12 p40. The highest levels of hCLF-1 mRNA were obs erved in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA de tected in a human kidney fibroblastic cell line. In fibroblast primary cell cultures, CLF-1 mRNA was up-regulated by TNF-alpha, IL-6, and IF N-gamma, Western blot analysis of recombinant forms of hCLF-1 showed t hat the protein has the tendency to form covalently linked di- and tet ramers, These results suggest that CLF-1 is a novel soluble cytokine r eceptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development.