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Proc Natl Acad Sci U S A. Sep 1986; 83(18): 6682–6686.
PMCID: PMC386573

Identification of a cyclic-AMP-responsive element within the rat somatostatin gene.

Abstract

We have examined the regulation of somatostatin gene expression by cAMP in PC12 rat pheochromocytoma cells transfected with the rat somatostatin gene. Forskolin at 10 microM caused a 4-fold increase in somatostatin mRNA levels within 4 hr of treatment in stably transfected cells. Chimeric genes containing the somatostatin gene promoter fused to the bacterial reporter gene encoding chloramphenicol acetyltransferase were also induced by cAMP in PC12 cells. To delineate the sequences required for response to cAMP, we constructed a series of promoter deletion mutants. Our studies defined a region between 60 and 29 base pairs upstream from the transcriptional initiation site that conferred cAMP responsiveness when placed adjacent to the simian virus 40 promoter. Within the cAMP-responsive element of the somatostatin gene, we observed an 8-base palindrome, 5'-TGACGTCA-3', which is highly conserved in many other genes whose expression is regulated by cAMP. cAMP responsiveness was greatly reduced when the somatostatin fusion genes were transfected into the mutant PC12 line A126-1B2, which is deficient in cAMP-dependent protein kinase 2. Our studies indicate that transcriptional regulation of the somatostatin gene by cAMP requires protein kinase 2 activity and may depend upon a highly conserved promoter element.

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Selected References

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  • Tapia-Arancibia L, Reichlin S. Vasoactive intestinal peptide and PHI stimulate somatostatin release from rat cerebral cortical and diencephalic cells in dispersed cell culture. Brain Res. 1985 Jun 10;336(1):67–72. [PubMed]
  • Shimatsu A, Kato Y, Matsushita N, Katakami H, Yanaihara N, Imura H. Effects of glucagon, Neurotensin, and vasoactive intestinal polypeptide on somatostatin release from perifused rat hypothalamus. Endocrinology. 1982 Jun;110(6):2113–2117. [PubMed]
  • Chihara K, Arimura A, Schally AV. Effect of intraventricular injection of dopamine, noreprinephrine, acetylcholine, and 5-hydroxytryptamine on immunoreactive somatostatin release into rat hypophyseal portal blood. Endocrinology. 1979 Jun;104(6):1656–1662. [PubMed]
  • Montminy MR, Low MJ, Tapia-Arancibia L, Reichlin S, Mandel G, Goodman RH. Cyclic AMP regulates somatostatin mRNA accumulation in primary diencephalic cultures and in transfected fibroblast cells. J Neurosci. 1986 Apr;6(4):1171–1176. [PubMed]
  • Tischler AS, Greene LA. Nerve growth factor-induced process formation by cultured rat pheochromocytoma cells. Nature. 1975 Nov 27;258(5533):341–342. [PubMed]
  • Lewis EJ, Tank AW, Weiner N, Chikaraishi DM. Regulation of tyrosine hydroxylase mRNA by glucocorticoid and cyclic AMP in a rat pheochromocytoma cell line. Isolation of a cDNA clone for tyrosine hydroxylase mRNA. J Biol Chem. 1983 Dec 10;258(23):14632–14637. [PubMed]
  • Greenberg ME, Greene LA, Ziff EB. Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells. J Biol Chem. 1985 Nov 15;260(26):14101–14110. [PubMed]
  • Guroff G, Dickens G, End D, Londos C. The action of adenosine analogs on PC12 cells. J Neurochem. 1981 Dec;37(6):1431–1439. [PubMed]
  • Van Buskirk R, Corcoran T, Wagner JA. Clonal variants of PC12 pheochromocytoma cells with defects in cAMP-dependent protein kinases induce ornithine decarboxylase in response to nerve growth factor but not to adenosine agonists. Mol Cell Biol. 1985 Aug;5(8):1984–1992. [PMC free article] [PubMed]
  • Greengard P. Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters. Nature. 1976 Mar 11;260(5547):101–108. [PubMed]
  • Montminy MR, Goodman RH, Horovitch SJ, Habener JF. Primary structure of the gene encoding rat preprosomatostatin. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3337–3340. [PMC free article] [PubMed]
  • Potter H, Weir L, Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. [PMC free article] [PubMed]
  • Patel YC, Reichlin S. Somatostatin in hypothalamus, extrahypothalamic brain, and peripheral tissues of the rat. Endocrinology. 1978 Feb;102(2):523–530. [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Laimins LA, Gruss P, Pozzatti R, Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. [PMC free article] [PubMed]
  • Maxam AM, Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. [PubMed]
  • Aron DC, Muszynski M, Birnbaum RS, Sabo SW, Roos BA. Somatostatin elaboration by monolayer cell cultures derived from transplantable rat medullary thyroid carcinoma: synergistic stimulatory effects of glucagon and calcium. Endocrinology. 1981 Dec;109(6):1830–1834. [PubMed]
  • Gorman CM, Merlino GT, Willingham MC, Pastan I, Howard BH. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. [PMC free article] [PubMed]
  • Shen LP, Rutter WJ. Sequence of the human somatostatin I gene. Science. 1984 Apr 13;224(4645):168–171. [PubMed]
  • Tavianini MA, Hayes TE, Magazin MD, Minth CD, Dixon JE. Isolation, characterization, and DNA sequence of the rat somatostatin gene. J Biol Chem. 1984 Oct 10;259(19):11798–11803. [PubMed]
  • Wynshaw-Boris A, Lugo TG, Short JM, Fournier RE, Hanson RW. Identification of a cAMP regulatory region in the gene for rat cytosolic phosphoenolpyruvate carboxykinase (GTP). Use of chimeric genes transfected into hepatoma cells. J Biol Chem. 1984 Oct 10;259(19):12161–12169. [PubMed]
  • Tsukada T, Horovitch SJ, Montminy MR, Mandel G, Goodman RH. Structure of the human vasoactive intestinal polypeptide gene. DNA. 1985 Aug;4(4):293–300. [PubMed]
  • Weaver CA, Gordon DF, Kissil MS, Mead DA, Kemper B. Isolation and complete nucleotide sequence of the gene for bovine parathyroid hormone. Gene. 1984 Jun;28(3):319–329. [PubMed]
  • Terao M, Watanabe Y, Mishina M, Numa S. Sequence requirement for transcription in vivo of the human preproenkephalin A gene. EMBO J. 1983;2(12):2223–2228. [PMC free article] [PubMed]
  • Darnell RB, Boime I. Differential expression of the human gonadotropin alpha gene in ectopic and eutopic cells. Mol Cell Biol. 1985 Nov;5(11):3157–3167. [PMC free article] [PubMed]
  • Van Beveren C, van Straaten F, Curran T, Müller R, Verma IM. Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini. Cell. 1983 Apr;32(4):1241–1255. [PubMed]
  • Thomsen DR, Stenberg RM, Goins WF, Stinski MF. Promoter-regulatory region of the major immediate early gene of human cytomegalovirus. Proc Natl Acad Sci U S A. 1984 Feb;81(3):659–663. [PMC free article] [PubMed]
  • Tsimanis A, Bichko V, Dreilina D, Meldrais J, Lozha V, Kukaine R, Gren E. The structure of cloned 3'-terminal RNA region of bovine leukemia virus (BLV). Nucleic Acids Res. 1983 Sep 10;11(17):6079–6087. [PMC free article] [PubMed]
  • Shimotohno K, Golde DW, Miwa M, Sugimura T, Chen IS. Nucleotide sequence analysis of the long terminal repeat of human T-cell leukemia virus type II. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1079–1083. [PMC free article] [PubMed]
  • Ono M, Ohishi H. Long terminal repeat sequences of intracisternal A particle genes in the Syrian hamster genome: identification of tRNAPhe as a putative primer tRNA. Nucleic Acids Res. 1983 Oct 25;11(20):7169–7179. [PMC free article] [PubMed]
  • Squinto SP, Kelley-Geraghty DC, Kuettel MR, Jungmann RA. Ultrastructural localization of cAMP-dependent protein kinase subunits in regenerating rat hepatocytes using immunogold electron microscopy. J Cyclic Nucleotide Protein Phosphor Res. 1985;10(1):65–73. [PubMed]
  • Constantinou AI, Squinto SP, Jungmann RA. The phosphoform of the regulatory subunit RII of cyclic AMP-dependent protein kinase possesses intrinsic topoisomerase activity. Cell. 1985 Sep;42(2):429–437. [PubMed]
  • Boney C, Fink D, Schlichter D, Carr K, Wicks WD. Direct evidence that the protein kinase catalytic subunit mediates the effects of cAMP on tyrosine aminotransferase synthesis. J Biol Chem. 1983 Apr 25;258(8):4911–4918. [PubMed]

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