Cytokine-like factor-1, a novel soluble protein, shares homology with members 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 identification and cloning of its murine homologue. They were identified from expressed sequence tags using amino acid sequences from conserved regions of the cytokine type I receptor family. Human CLF-1 and murine CLF-1 shared 96% amino acid identity and significant homology with many cytokine type I receptors. CLF-1 is a secreted protein, suggesting that it is either a soluble subunit within a cytokine receptor complex, like the 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 observed in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA detected in a human kidney fibroblastic cell line. In fibroblast primary cell cultures, CLF-1 mRNA was up-regulated by TNF-alpha, IL-6, and IFN-gamma. Western blot analysis of recombinant forms of hCLF-1 showed that the protein has the tendency to form covalently linked di- and tetramers. These results suggest that CLF-1 is a novel soluble cytokine receptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development.
Elson
G C
GC
Department of Immunology, Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, Plan-les-Ouates, Switzerland.
Graber
P
P
Losberger
C
C
Herren
S
S
Gretener
D
D
Menoud
L N
LN
Wells
T N
TN
Kosco-Vilbois
M H
MH
Gauchat
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D016466:CHO Cells; D017124:Conserved Sequence; D006224:Cricetinae; D005091:Exons; D006801:Humans; D007438:Introns; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; C113554:cytokine-like factor-1