c-Src activates the DNA binding and transcriptional activity of Stat3 molecules: serine 727 is not required for transcriptional activation under certain circumstances.
Stat3 proteins are constitutively activated in cells transformed by v-Src and the proteins have been shown to interact directly. Subsequent studies have shown that Stat3 is required for cellular transformation of NIH fibroblasts by v-Src, suggesting a potential role for Stat3 in aberrant cell growth. Stat3 is phosphorylated on a single tyrosine (tyrosine 705) which is required for effective dimer formation. An additional phosphorylation event (serine 727) is believed to be required for full transcriptional activity of Stat1 and Stat3 molecules. Here we report that c-Src activates the DNA binding activity of Stat3alpha, Stat3beta, and three Stat3 mutants, one in which serine 727 was replaced by alanine (Stat3alphaS727A) and C-terminal truncated molecules Delta48 and Delta55. Consistent with this finding is a general increase in the tyrosine 705-phosphorylated Stat3 in cells cotransfected with c-Src. Furthermore, transcription from an alpha-2 macroglobulin reporter gene is activated by Stat3alphaS727A to the same magnitude as compared to Stat3alpha and Stat3beta in the presence of c-Src. These results suggest that serine 727, contained in a consensus MAP kinase recognition site and shown to be the only serine in Stat3 phosphorylated in epidermal growth factor (EGF) treated cells, is not necessary for transcriptional activity comparable to wild-type Stat3alpha or Stat3beta when activated by c-Src in COS-7 cells.
Schaefer
L K
LK
Department of Neurosurgery, Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Wang
S
S
Schaefer
T S
TS
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D017930:Genes, Reporter; D016758:Genes, jun / Q000235:genetics; D016391:Genes, src / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D017384:Sequence Deletion; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D004815:Epidermal Growth Factor