Highly conserved amino-acid sequence between murine STAT3 and a revised human STAT3 sequence.
Signal transducer and activator of transcription 3 (STAT3) is an important mediator of cytokine signaling, whose cDNA and protein sequences have been fully characterized. We sequenced the whole human STAT3 cDNA isolated from HepG2 cells. The new sequence determined contains 43 nucleotide changes overall, corresponding to six modifications at the amino-acid level. The revised amino-acid sequence of human STAT3 is now completely identical to the mouse sequence, except for a single amino-acid change at position 760. Thus STAT3 now results as one of the most evolutionarily conserved among known proteins. By using specific RT-PCR we could discriminate between the original sequence and the new variant. Amplification of regions within the src-homology domain 2 (SH2) of STAT3, from the RNAs of 11 different tissues or cells, revealed only the expression of the new SH2 variant. Besides, only this SH2 variant was amplified from human genomic DNA. We conclude that the new sequence we have determined in this study represents a revised sequence of hSTAT3 or, less likely, a new predominant allele.
Pietra
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Drug Discovery Department, Istituto di Ricerca Cesare Serono, 22 Via di Valle Caia, 00040 Ardea, Rome, Italy.
Bressan
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Pezzotti
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AR
Serlupi-Crescenzi
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D005796:Genes; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000235:genetics; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators