Molecular cloning and nucleotide sequence of the human growth hormone structural gene

Roskam, Willem; Rougeon, F

doi:10.1093/nar/7.2.305

Cited by 65 publications

(15 citation statements)

References 54 publications

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“…The hGH gene encodes an 825-bp mRNA which is interrupted by four introns (13,43). This gene has been isolated within a 2.6-kb EcoRI fragment such that the coding sequences and introns are flanked by 500 bp of 5' DNA and 525 bp of 3' flanking DNA (13,46).…”

Section: Resultsmentioning

confidence: 99%

Glucocorticoids enhance stability of human growth hormone mRNA.

Paek¹,

Axel²

1987

Mol. Cell. Biol.

260

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We have studied the control of expression of the human growth hormone (hGH) Steroid hormones regulate gene expression by associating with receptor proteins which then interact with specific DNA sequences in the chromosome (for a review, see reference 60). The glucocorticoid receptor, for example, binds to specific sites in several hormone-responsive genes, and this interaction presumably results in enhanced transcription upon exposure to glucocorticoid hormones (for reviews, see references 41 and 59). However, the effects of steroid hormones on gene expression are not restricted to transcriptional events (6,20,35,51). Estrogen, for example, results in a 1,000-fold increase in the transcription of the viteilogenin gene in Xenopus laevis liver but also exerts a profound effect on the stability of vitellogenin mRNA (6). Given the specificity with which estrogen enhances the stability of vitellogenin mRNA, it is likely that sequences reside within this mRNA which are responsive to the hormone and increase the expression of this gene via posttranscriptional mechanisms.Expression of the growth hormone (GH) genes is restricted to somatotrophs of the anterior pituitary (26) and is regulated by the hypothalamic growth hormone releasing factor (3, 4, 22) and glucocorticoid and thyroid hormones.'In cultures of rat pituitary cells (GH3 and GC [2, 61]), either glucocorticoid or thyroid hormone increases the level of the GH mRNAs and a synergism is observed when these two hormones are added together (32,45,47,50,53). Thyroid hormone increases the rate of transcription of the rat GH gene in pituitary cell lines (12,14,19,38,49,58), and the regulatory element responsive to thyroid hormone has been identified within the 5' flanking sequences of the rat GH gene (8,12 However, the level of transcriptional activation in the presence of glucocorticoids observed in vitro in nuclear transcription assays is significantly lower than the steady-state level of induction of GH mRNA in the rat pituitary cells, suggesting that posttranscriptional events, mediated by steroids, may also be operative (49).In previous studies, we have introduced the human GH (hGH) gene into murine fibroblasts and demonstrated that hGH mRNA is inducible by glucocorticoids (42). To localize the sequences responsible for induction and to determine the mechanism by which these cis-acting sequences enhance gene expression, we have now constructed a series of fusion genes between hGH and the herpes simplex virus (HSV) thymidine kinase (tk) gene. We observed that a gene consisting of hGH cDNA sequences, driven by a tk promoter and flanked by 3' tk DNA, is inducible in transformed fibroblasts. Further, this induction results at least in part from changes in mRNA stability, suggesting that glucocorticoids regulate hGH expression at the level of RNA stability as well as RNA synthesis. MATERIALS AND METHODSCell culture and hormonal induction. Mouse Ltk-aprtcells were maintained as described previously (56), and Ltkaprt+ transformants were selected and mnaintained in Dulb...

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Section: Resultsmentioning

confidence: 99%

Glucocorticoids enhance stability of human growth hormone mRNA.

Paek¹,

Axel²

1987

Mol. Cell. Biol.

260

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“…Detailed studies of GH action have been possible because GH itself was cloned over 20 years ago [26], [27] [28] and the GH receptor (GHR) was cloned shortly thereafter [29], [30]. The human GHR (hGHR) is a type I transmembrane protein of 687 residues that has no sequence homology with known kinases in its cytoplasmic region.…”

Section: Gh-mediated Stimulationmentioning

confidence: 99%

Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

Redelman¹,

Taub

et al. 2008

Cellular Immunology

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Neuroendocrine hormones such as growth hormone (GH) and prolactin (PRL) have been demonstrated to accelerate the recovery of the immune response after chemotherapy and bone marrow transplantation and to enhance the restoration of immunity in individuals infected with HIV and in normal individuals with compromised immune systems associated with aging. As the mechanism of action of these hormones has been elucidated, it has become clear that they are integral members of the immunological cytokine/chemokine network and share regulatory mechanisms with a wide variety of cytokines and chemokines. The members of this cytokine network induce and can be regulated by members of the suppressor of cytokine signaling (SOCS) family of intracellular proteins. In order to take advantage of the potential beneficial effects of hormones such as GH or PRL, it is essential to take into consideration the overall cytokine network and the regulatory effects of SOCS proteins.

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“…(c) The fold typical of the interferon-like subfamily, whose structurally known members include interferon-P (IFN-[) [43] and interferon-y (IFN-y) [44,45]. Key elements include a helix in the C-D crossover and an A-B crossover connection that passes in front of helix D. (d) Exon structures of the structurally known members of each subfamily (references in the order of appearance: [46][47][48][49][50][51][52][53][54][55]). The major helices (striped) and P-strands (shaded) are indicated and labeled as in (a)-(c).…”

Section: Introductionmentioning

confidence: 99%

Structural comparisons among the short-chain helical cytokines

et al. 1994

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Background: Cytokines and growth factors are soluble proteins that regulate the development and activities of many cell types. One group of these proteins have structures based on a four-helix bundle, though this similarity is not apparent from amino acid sequence comparisons. An understanding of how diverse sequences can adopt the same fold would be useful for recognizing and aligning distant homologs and for applying structural information gained from one protein to other sequences. Results: We have approached this problem by comparing the five known structures which adopt a granulocytemacrophage colony-stimulating factor (GM-CSF)-like, or short-chain fold: interleukin (IL)-4, GM-CSF, IL-2, IL-5, and macrophage colony-stimulating factor. The comparison reveals a common structural framework of five segments including 31 inner-core and 30 largely exposed residues. Buried polar interactions found in each protein illustrate how complementary substitutions maintain protein stability and may help specify unique core packing. A profile based on the known structures is not sufficient to guarantee accurate amino acid sequence alignments with other family members. Comparisons of the conserved short-chain framework with growth hormone define the optimal structural alignment. Conclusions: Our results are useful for extrapolating functional results among the short-chain cytokines and growth hormone, and provide a foundation for similar characterization of other subfamilies. These results also show that the placement of polar residues at different buried positions in each protein complicates sequence comparisons, and they document a challenging test case for methods aimed at recognizing and aligning distant homologs. 1994, 2:159-173 Structure 15 March

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Molecular cloning and nucleotide sequence of the human growth hormone structural gene

Cited by 65 publications

References 54 publications

Glucocorticoids enhance stability of human growth hormone mRNA.

Glucocorticoids enhance stability of human growth hormone mRNA.

Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

Structural comparisons among the short-chain helical cytokines

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