Computational EST database analysis identifies a novel member of the neuropoietic cytokine family.
A novel member of the neuropoietic cytokine family has been cloned and the protein expressed and characterized. In an effort to identify novel secreted proteins, an algorithm incorporating neural network algorithms was applied to a large EST database. A full-length clone was identified that is 1710 bp in length and has a single open reading frame of 225 amino acids. This new cytokine is most homologous to cardiotrophin-1, having a similarity and an identity of 46 and 29%, respectively, and therefore we have named it cardiotrophin-like cytokine (CLC). Northern hybridization analysis identified a 1.4-kb messenger RNA that is highly expressed in spleen and peripheral leukocytes. Purified recombinant CLC induced the activation of NFkappaB and SRE reporter constructs in the TF-1, U937, and M1 cell lines. Furthermore, the signal transduction pathway for CLC was characterized in the neuroblastoma cell line SK-N-MC and found to involve tyrosine phosphorylation of gp130 and STAT-1.
Shi
Y
Y
Department of Molecular Biology, Department of Pharmacology, Department of Protein Expression, Human Genome Sciences, Inc., 9410 Key West Avenue, Rockville, Maryland 20850, USA.
Wang
W
W
Yourey
P A
PA
Gohari
S
S
Zukauskas
D
D
Zhang
J
J
Ruben
S
S
Alderson
R F
RF
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003001:Cloning, Molecular; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D016208:Databases, Factual; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016571:Neural Networks, Computer; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D050794:STAT1 Transcription Factor; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; C121169:cardiotrophin-like cytokine; D050822:Cytokine Receptor gp130; D019000:Phosphotyrosine; C092073:cardiotrophin 1