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(Received for publication, June 29, 1994; and in revised form, December 2, 1994)
The mechanisms by which the binding of growth hormone (GH) to
its cell surface receptor elicits changes in gene transcription are
largely unknown. The transcription factor Stat1/p91 has been shown to
be activated by GH. Here we show that acute phase response factor or
Stat3 (or an antigenically related protein), is also activated by GH.
Stat3 has been implicated in the interleukin-6-dependent induction of
acute phase response genes. GH promotes in 3T3-F442A fibroblasts the
tyrosyl phosphorylation of a protein immunoprecipitated by antibodies
to Stat3. This protein co-migrates with a tyrosyl phosphorylated
protein from cells treated with leukemia inhibitory factor, a cytokine
known to activate Stat3. Tyrosyl phosphorylated Stat3 is also observed
in response to interferon-
. Stat3 is present in GH-inducible
DNA-binding complexes that bind the sis-inducible element in
the c-fos promoter and the acute phase response element in the
-macroglobulin promoter. The ability of GH to activate
both Stat1 and Stat3 (i.e. increase their tyrosyl
phosphorylation and ability to bind to DNA) suggests that gene
regulation by GH involves multiple Stat proteins. Shared transcription
factors among hormones and cytokines that activate JAK kinases provide
an explanation for shared responses, while the ability of the different
ligands to differentially recruit various Stat family members suggests
mechanisms by which specificity in gene regulation could be achieved.
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C. Ohlsson, B.-A. Bengtsson, O. G. P. Isaksson, T. T. Andreassen, and M. C. Slootweg Growth Hormone and Bone Endocr. Rev., February 1, 1998; 19(1): 55 - 79. [Abstract] [Full Text]
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Z. Zhang, S. Jones, J. S. Hagood, N. L. Fuentes, and G. M. Fuller STAT3 Acts as a Co-activator of Glucocorticoid Receptor Signaling J. Biol. Chem., December 5, 1997; 272(49): 30607 - 30610. [Abstract] [Full Text] [PDF]
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H. Kodama, K. Fukuda, J. Pan, S. Makino, A. Baba, S. Hori, and S. Ogawa Leukemia Inhibitory Factor, a Potent Cardiac Hypertrophic Cytokine, Activates the JAK/STAT Pathway in Rat Cardiomyocytes Circ. Res., November 19, 1997; 81(5): 656 - 663. [Abstract] [Full Text]
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J. Liao, C. Hodge, D. Meyer, P. S. Ho, K. Rosenspire, and J. Schwartz Growth Hormone Regulates Ternary Complex Factors and Serum Response Factor Associated with the c-fos Serum Response Element J. Biol. Chem., October 10, 1997; 272(41): 25951 - 25958. [Abstract] [Full Text] [PDF]
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