The serum response element can mediate induction of c-fos by growth hormone.

Abstract

The c-fos protooncogene is transcriptionaily activated by a wide variety of agents including serum, growth factors, and phorbol esters. This induction is rapid and transient and is mediated through a number of identified promoter elements. Growth hormone (GH) is also known to induce transcription of c-fos in a variety of cell tpes including NIH 3T3 fibroblasts and 3T3-F442A preadipocytes. To identify DNA sequences in the c-fos gene regulated by GH, this study sought to determine whether induction of c-fos by GH involves previously identified c-fos promoter elements. A plasmid containing a growth factor-sensitive fragment of the upstream region of the c-fos promoter from -361 to -264 bp was tested for GH sensitivity. The fragment was cloned upstream of a human c-fos reporter [designated FOS by Human Gene Mapping 11 (1991)] , which included basal promoter elements. In transiently transfected mouse NIB 3T3 fibroblasts, the promoter fragment conferred GH sensitivity on the human c-fos reporter. To identify a specific GH-sensitive DNA sequence in this promoter, a serum response element (SRE)-reporter plasmid was tested and found to be stimulated by GH. GH was effective in inducing expression through the SRE over a range of physiological GH concentrations. Since GH was recently found to synergize with serum factors in inducing c-fos transcription, the effect of GH and serum on SRE function was examined for insight into the mechanism for such synergism. The combined effect of GH and serum to induce reporter expression through the SRE was greater than the added effects of GH and serum, indicating that the synergism between GH and serum in inducing c-fos involves the SRE sequence. These studies identify the SRE as one specific DNA sequence in the c-fos promoter functionally regulated by GH. It is notable that GH is effective at physiological concentrations. Furthermore, synergism in c-fos induction between GH and serum factors is evident through the SRE.

Acute Control of Insulin-like Growth Factor-I Gene Transcription by Growth Hormone through Stat5b

“…GH also rapidly activates other genes in vivo through additional signal transduction pathways. As seen in this report, the early-response gene, c-fos, is induced with kinetics similar to those of IGF-I, but as expected is unmodified by dominant-negative or constitutively active Stat5b, because previous studies have demonstrated that c-fos gene transcription is stimulated by GH through pathways involving Stats 1 and 3, and the Erk-activated Elk-1 transcription factor (28,32,33).…”

Signalling Pathway of GH.

“…In 3T3-F442A fibroblasts, CHO and COS cells expressing cloned rat liver GH receptor, and livers from hypophysectomized rats, GH was found to stimulate the binding of Stats 1, 3 and 5 [15][16][17][18][19][20]. No phosphorylation of Stat2 was observed [21]. Consistent with Stats 1, 3 and 5 serving as signalling molecules for GH, GH was also shown to promote the binding of Stats 1, 3 and 5 to DNA.…”

Cloning and characterization of the rat gene for the acid-labile subunit of the insulin-like growth factor binding protein complex

“…Activation of gene transcription by GH also can be mediated through other types of cis element. For example, GH rapidly activates transcription of the early response gene c-fos through a sequence known as the serum response element (SRE), and of the serine protease inhibitor (Spi) 2·1 gene through purine-rich sequences (Le Cam et al 1994, Meyer et al 1993. The trans acting factors that bind to these cis elements are probably unrelated to the STAT proteins.…”