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 a nd metabolism are unknown, We have demonstrated previously that in viv o GH treatment rapidly stimulates the tyrosine phosphorylation of mult iple nuclear proteins and have identified the inducible transcription factor Stat1 (formerly Stat91) as one of the major GH-activated nuclea r phosphoproteins. We now show that Stat3, a new member of the STAT (s ignal transducer and activator of transcription) family of transcripti on factors, is also phosphorylated on tyrosine residues and rapidly ap pears in the nucleus in response to GH. Activated Stat3 interacts with the naturally occurring c-sis-inducible element of the c-fos gene aft er 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-ind ucible element is used as a probe, Our results suggest that multiple S TAT proteins may mediate some of the pleiotropic effects of GH on gene expression.