In vivo growth hormone treatment rapidly stimulates the tyrosine phosphorylation and activation of Stat3.
The mechanisms by which GH regulates gene expression to alter growth and metabolism are unknown. We have demonstrated previously that in vivo GH treatment rapidly stimulates the tyrosine phosphorylation of multiple nuclear proteins and have identified the inducible transcription factor Stat1 (formerly Stat91) as one of the major GH-activated nuclear phosphoproteins. We now show that Stat3, a new member of the STAT (signal transducer and activator of transcription) family of transcription factors, is also phosphorylated on tyrosine residues and rapidly appears in the nucleus in response to GH. Activated Stat3 interacts with the naturally occurring c-sis-inducible element of the c-fos gene after GH treatment, as demonstrated by gel mobility shift assay, and is a component of gel-shifted bands A and B when the high affinity sis-inducible element is used as a probe. Our results suggest that multiple STAT proteins may mediate some of the pleiotropic effects of GH on gene expression.
Gronowski
A M
AM
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Zhong
Z
Z
Wen
Z
Z
Thomas
M J
MJ
Darnell
J E
JE
Rotwein
P
P
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000235:genetics; D013006:Growth Hormone / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D013268:Stimulation, Chemical; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014443:Tyrosine; D013006:Growth Hormone