Growth Hormone Activation of Stat 1, Stat 3, and Stat 5 in Rat Liver

作者：Prabha Agrawal Ram, Soo-Hee Park, Hee Kyoung Choi, David J. Waxman · 发表于：Journal of Biological Chemistry · 年份：1996 · DOI：10.1074/jbc.271.10.5929 · 被引用次数：230 · 研究领域：Cytokine Signaling Pathways and Interactions、Growth Hormone and Insulin-like Growth Factors、Reproductive System and Pregnancy

Intermittent plasma growth hormone (GH) pulses, which occur in male but not female rats, activate liver Stat 5 by a mechanism that involves tyrosine phosphorylation and nuclear translocation of this latent cytoplasmic transcription factor (Waxman, D. J., Ram, P. A., Park, S. H., and Choi, H. K. (1995) J. Biol. Chem. 270, 13262-13270). We demonstrate that physiological levels of GH can also activate Stat 1 and Stat 3 in liver tissue, but with a dependence on the dose of GH and its temporal plasma profile that is distinct from Stat 5 and with a striking desensitization following a single hormone pulse that is not observed with liver Stat 5. GH activation of the two groups of Stats leads to their selective binding to DNA response elements upstream of the c-fos gene (c-sis-inducible enhancer element; Stat 1 and Stat 3 binding) and the beta-casein gene (mammary gland factor element; liver Stat 5 binding). In addition to tyrosine phosphorylation, GH is shown to stimulate phosphorylation of these Stats on serine or threonine in a manner that either enhances (Stat 1 and Stat 3) or substantially alters (liver Stat 5) the binding of each Stat to its cognate DNA response element. These findings establish the occurrence of multiple, Stat-dependent GH signaling pathways in liver cells that can target distinct genes and thereby contribute to the diverse effects that GH and its sexually dimorphic plasma profile have on liver gene expression.