Zebrafish stat3 is expressed in restricted tissues during embryogenesis and stat1 rescues cytokine signaling in a STAT1-deficient human cell line.
Transcription factors of the STAT family are required for cellular responses to multiple signaling molecules. After ligand binding-induced activation of cognate receptors, STAT proteins are phosphorylated, hetero- or homodimerize, and translocate to the nucleus. Subsequent STAT binding to specific DNA elements in the promoters of signal-responsive genes alters the transcriptional activity of these loci. STAT function has been implicated in the transduction of signals for growth, reproduction, viral defense, and immune regulation. We have isolated and characterized two STAT homologs from the zebrafish Danio rerio. The stat3 gene is expressed in a tissue-restricted manner during embryogenesis, and larval development with highest levels of transcript are detected in the anterior hypoblast, eyes, cranial sensory ganglia, gut, pharyngeal arches, cranial motor nuclei, and lateral line system. In contrast, the stat1 gene is not expressed during early development. The stat3 gene maps to a chromosomal position syntenic with the mouse and human STAT3 homologs, whereas the stat1 gene does not. Despite a higher rate of evolutionary change in stat1 relative to stat3, the stat1 protein rescues interferon-signaling functions in a STAT1-deficient human cell line, indicating that cytokine-signaling mechanisms are likely to be conserved between fish and tetrapods. Dev Dyn 1999;215:352-370.
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia. aoates@molbio.princeton.edu
A C
AC
Oates
P
P
Wollberg
S J
SJ
Pratt
B H
BH
Paw
S L
SL
Johnson
R K
RK
Ho
J H
JH
Postlethwait
L I
LI
Zon
A F
AF
Wilks
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism; D002874:Chromosome Mapping; D002875:Chromosomes; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology; D019143:Evolution, Molecular; D006801:Humans; D053613:Janus Kinase 1; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D017933:Peripheral Nervous System / Q000378:metabolism; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D029961:Zebrafish Proteins; C494083:stat1a protein, zebrafish; C494089:stat3 protein, zebrafish; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; C507907:jak1 protein, zebrafish