Regulation of Stat3 transcriptional activity by the conserved LPMSP motif for OSM and IL-6 signaling.
To achieve maximal transcriptional activity in response to gp130 cytokines, Serine-727 (Ser-727) of Stat3 is phosphorylated. Ser-727 resides in the LPMSP motif, the only conserved sequence among the transcription activation domains of several STATs. We show here that in addition to Ser-727, other residues in this LPMSP motif are also required for Stat3 activity in response to cytokine signaling through regulation of Ser-727 phosphorylation and recruitment of the transcription co-activator CBP/p300 to the promoters of Stat3-target genes for transcription activation. Hence, we have demonstrated a critical role for the whole conserved LPMSP motif in JAK-STAT signaling.
Sun
Wei
W
Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Snyder
Marylynn
M
Levy
David E
DE
Zhang
J Jillian
JJ
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D053683:Oncostatin M / Q000494:pharmacology*; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection
D017931:DNA Primers; D015850:Interleukin-6; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053683:Oncostatin M; D012694:Serine; D011392:Proline