Tissue-Specific Enhancer of the Human Glycoprotein Hormone α-Subunit Gene: Dependence on Cyclic AMP-Inducible Elements

Delegeane, A M; Ferland, Louis H.; Mellon, Pamela L.

doi:10.1128/mcb.7.11.3994-4002.1987

Cited by 17 publications

(12 citation statements)

References 39 publications

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“…In the transfection, a 5:5:1 ratio of reporter, receptor, and neo marker plasmids was used. The reporter plasmid was derived from pXP1 (50) and consists of a cAMP response element enhancer, a synthetic pentameric CREB binding enhancer from VIP, and a human glycoprotein hormone R-subunit promoter attached 5′ to luciferase cDNA (51,52). The sequence of the enhancer and promoter region have been deposited in GenBank under accession number AF047543 (A.P.-T. and A.K., unpublished results).…”

Section: Measurement Of the Inhibition Of Adenylate Cyclase By Camp-d...mentioning

confidence: 99%

Identification of Surface Residues of the Monocyte Chemotactic Protein 1 That Affect Signaling through the Receptor CCR2

Jarnagin¹,

Grünberger²,

Mulkins³

et al. 1999

Biochemistry

106

107

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The CC chemokine, monocyte chemotactic protein, 1 (MCP-1) functions as a major chemoattractant for T-cells and monocytes by interacting with the seven-transmembrane G protein-coupled receptor CCR2. To identify which residues of MCP-1 contribute to signaling though CCR2, we mutated all the surface-exposed residues to alanine and other amino acids and made some selective large changes at the amino terminus. We then characterized the impact of these mutations on three postreceptor pathways involving inhibition of cAMP synthesis, stimulation of cytosolic calcium influx, and chemotaxis. The results highlight several important features of the signaling process and the correlation between binding and signaling: The amino terminus of MCP-1 is essential as truncation of residues 2-8 ([1+9-76]hMCP-1) results in a protein that cannot stimulate chemotaxis. However, the exact peptide sequence may be unimportant as individual alanine mutations or simultaneous replacement of residues 3-6 with alanine had little effect. Y13 is also important and must be a large nonpolar residue for chemotaxis to occur. Interestingly, both Y13 and [1+9-76]hMCP-1 are high-affinity binders and thus affinity of these mutants is not correlated with ability to promote chemotaxis. For the other surface residues there is a strong correlation between binding affinity and agonist potency in all three signaling pathways. Perhaps the most interesting observation is that although Y13A and [1+9-76]hMCP are antagonists of chemotaxis, they are agonists of pathways involving inhibition of cAMP synthesis and, in the case of Y13A, calcium influx. These results demonstrate that these two well-known signaling events are not sufficient to drive chemotaxis. Furthermore, it suggests that specific molecular features of MCP-1 induce different conformations in CCR2 that are coupled to separate postreceptor pathways. Therefore, by judicious design of antagonists, it should be possible to trap CCR2 in conformational states that are unable to stimulate all of the pathways required for chemotaxis.

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Section: Measurement Of the Inhibition Of Adenylate Cyclase By Camp-d...mentioning

confidence: 99%

Identification of Surface Residues of the Monocyte Chemotactic Protein 1 That Affect Signaling through the Receptor CCR2

Jarnagin¹,

Grünberger²,

Mulkins³

et al. 1999

Biochemistry

106

107

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“…Deletion of one GC box (CNP3CAT) and two GC boxes (CNP2CAT) caused 60 and 90% decreases in activity, respectively, and deletion of GC boxes and the CRE-like sequence led to a 99% decrease. CRE sequences have been identified in the promoter regions of several genes expressed in a pituitary-specific manner, including transcription factor Pit-1/GHF1 (3,5,22). No significant increase in CAT activity was observed when GH3 cells transfected with CNP6CAT or CNP12CAT were treated with either forskolin The transcription start site was determined by primer extension and riboprobe mapping of total RNA from GH3 cells transfected with CNP6CAT.…”

Section: Resultsmentioning

confidence: 99%

Cell-Type-Specific Function of the C-Type Natriuretic Peptide Gene Promoter in Rat Anterior Pituitary-Derived Cultured Cell Lines

Ohta

Shimekake

Nagata

1993

Molecular and Cellular Biology

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The promoter function of the human C-type natriuretic peptide (CNP) gene in various cultured cells was examined by transient transfection assays. The CNP promoter functioned very effectively in GH3 cells, which originated from the growth hormone-producing tumor of the rat anterior pituitary and somatomammotroph phenotype, but functioned much less effectively in GH1 cells, another type of rat pituitary-derived cell with a somatotroph phenotype, and rat primary cardiocytes. The CNP promoter did not function at all in other cells, including AtT20 cells of murine pituitary corticotroph origin. Functional analyses of the deleted promoters with various 5' deletion breakpoints revealed the existence of at least two negative and one positive regulatory regions. Within the positive regulatory region (positions -54 to -19), which conferred 90% of the promoter activity in GH3 cells, two equipotent GC-rich cis elements (positions -49 to -45 and -40 to -35) were identified. Both sites shared half of the promoter activity and binding properties to the nuclear protein in GH3 cells. Rat anterior pituitary tissue contained the binding protein of the identified cis element, which was identical or similar to that of GH3 cells. With Southwestern (DNA-protein) analysis, a 70-kDa specific binding protein distinct from known factors such as SP-1, AP-2, and Pit-1 was identified in the nuclear extract of GH3 cells.

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“…ATF-43 to ATF-43-CREB complexes varied dramatically among different cell types (Fig. 6), as does the activity of several cAMP response elements (2,16,17,38,49,80,90).…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanisms by which a variety of transcriptional responses are generated from groups of factors with apparently indiscriminate DNA-binding activity are not yet clear. Promoter elements containing the critical core motif CGTCA (referred to here as activating transcription factor [ATF]-binding sites) are important for the activity of several promoters that respond to different signals. ATF-binding sites are implicated in positive control by the adenovirus Ela protein (7,9,31,40,56,57,88,102) and intracellular cyclic AMP (cAMP) (2,14,17,19,26,38,59,71,80,82,84,87,94) and may also be involved in the function of enhancer elements that respond to the human T-cell lymphotropic virus type I (HTLV-1) transactivator p40tax (10,28,30,45,69,72) and the bovine leukemia virus transactivator p38tax (51). In addition, the hydroxymethylglutaryl (HMG)-coenzyme A reductase and 1-DNA polymerase promoters contain ATF-binding sites and are under negative control by sterols (74) and p4Otax (46,99), respectively.…”

mentioning

confidence: 99%

The Cellular Transcription Factor CREB Corresponds to Activating Transcription Factor 47 (ATF-47) and Forms Complexes with a Group of Polypeptides Related to ATF-43

Hurst

Masson

Jones

et al. 1990

Molecular and Cellular Biology

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Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We demonstrated that CREB and ATF-47 are identical and that CREB and ATF-43 form protein-protein complexes. We also found that the cis requirements for stable DNA binding by ATF-43 and CREB are different. Using antibodies to ATF-43 we have identified a group of polypeptides (ATF-43) in the size range from 40 to 43 kDa. ATF-43 polypeptides are related by their reactivity with anti-ATF-43, DNA-binding specificity, complex formation with CREB, heat stability, and phosphorylation by protein kinase A. Certain cell types vary in their ATF-43 complement, suggesting that CREB activity is modulated in a cell-type-specific manner through interaction with ATF-43. ATF-43 polypeptides do not appear simply to correspond to the gene products of the ATF multigene family, suggesting that the size of the ATF family at the protein level is even larger than predicted from cDNA-cloning studies.

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Tissue-Specific Enhancer of the Human Glycoprotein Hormone α-Subunit Gene: Dependence on Cyclic AMP-Inducible Elements

Cited by 17 publications

References 39 publications

Identification of Surface Residues of the Monocyte Chemotactic Protein 1 That Affect Signaling through the Receptor CCR2

Identification of Surface Residues of the Monocyte Chemotactic Protein 1 That Affect Signaling through the Receptor CCR2

Cell-Type-Specific Function of the C-Type Natriuretic Peptide Gene Promoter in Rat Anterior Pituitary-Derived Cultured Cell Lines

The Cellular Transcription Factor CREB Corresponds to Activating Transcription Factor 47 (ATF-47) and Forms Complexes with a Group of Polypeptides Related to ATF-43

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