Synergistic increase in c-fos expression by simultaneous activation of the ras/raf/map kinase- and protein kinase A signaling pathways is mediated by the c-fos AP-1 and SRE sites

Seternes, Ole Morten; Sørensen, Rita; Johansen, Bjarne; Loennechen, Thrina; Aarbakke, Jarle; Moens, Ugo

doi:10.1016/s0167-4781(97)00189-9

Cited by 23 publications

(13 citation statements)

References 66 publications

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“…4B), and the c-fos proto-oncogene (Fig. 9C), which requires Elk1 in the formation of a ternary complex at the c-fos serum response element (34,49,61,73,81,82). Potentiated ERK activation induced by EGF and forskolin in JEG3 cells is reminiscent of the situation in some prostate cancer cell lines, in which the combined actions of EGF and inducers of cAMP such as forskolin result in similar ERK potentiation (15,62).…”

Section: Discussionmentioning

confidence: 82%

Role of the Cyclic AMP Response Element Binding Complex and Activation of Mitogen-Activated Protein Kinases in Synergistic Activation of the Glycoprotein Hormone α Subunit Gene by Epidermal Growth Factor and Forskolin

Roberson

Ban

Zhang

et al. 2000

Molecular and Cellular Biology

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The aim of these studies was to elucidate a role for epidermal growth factor (EGF) signaling in the transcriptional regulation of the glycoprotein hormone ␣ subunit gene, a subunit of chorionic gonadotropin. Studies examined the effects of EGF and the adenylate cyclase activator forskolin on the expression of a transfected ␣ subunit reporter gene in a human choriocarcinoma cell line (JEG3). At maximal doses, administration of EGF resulted in a 50% increase in a subunit reporter activity; forskolin administration induced a fivefold activation; the combined actions of EGF and forskolin resulted in synergistic activation (greater than eightfold) of the ␣ subunit reporter. Mutagenesis studies revealed that the cyclic AMP response elements (CRE) were required and sufficient to mediate EGF-forskolin-induced synergistic activation. Chorionic gonadotropin (CG) is a heterodimeric glycoprotein hormone consisting of an ␣ subunit common to other glycoprotein hormone family members noncovalently linked to a CG-specific ␤ subunit (58). CG is synthesized and secreted by placental syncytiotrophoblast cells during the first trimester of pregnancy in women and nonhuman primates. CG is a luteotropin required for maintenance of progesterone production by the ovarian corpus luteum in early gestation. An important factor in the establishment of early pregnancy appears to be the timing and rate of increase in the secretion of CG that is highly correlated with a rise in progesterone levels in peripheral circulation (42). Insufficient progesterone production during early pregnancy is correlated with the potential for early or recurrent pregnancy loss in women (6, 7, 27, 47). Thus, endocrine mechanisms that potentiate the synthesis of CG subunits and CG secretion are essential for the establishment of pregnancy. Despite the clear importance of CG to early pregnancy, the specific ligands and signaling mechanisms that regulate the expression of CG subunit genes in placental cells have not been fully elucidated.The ␣ subunit of the glycoprotein hormones is a unique and useful transcriptional model for the study of tissue-specific gene expression because the ␣ subunit gene is expressed in placental and pituitary cells, albeit by various mechanisms. Analysis of the architecture of the ␣ subunit promoter revealed the presence of multiple promoter elements that are required for transcriptional regulation. These include the pituitary glycoprotein hormone basal element, which binds members of the LIM class of homeobox-containing proteins (67,71,72); the ␣ basal element (32); the gonadotrope-specific element, which binds steroidogenic factor 1 (9, 36); the upstream regulatory element (URE) (12,26,38,59); the GATA element, which binds several GATA factors (75); the dual tandem cyclic AMP (cAMP) response elements (CREs), which bind CRE binding protein (CREB) (5,10,12,13,22,25,32,35,52,59,74); the junctional regulatory element (JRE) (4, 12); and a unique CAAT box (12,40). Extensive mutagenesis studies have begun to unravel the specific requirements f...

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Section: Discussionmentioning

confidence: 82%

Role of the Cyclic AMP Response Element Binding Complex and Activation of Mitogen-Activated Protein Kinases in Synergistic Activation of the Glycoprotein Hormone α Subunit Gene by Epidermal Growth Factor and Forskolin

Roberson

Ban

Zhang

et al. 2000

Molecular and Cellular Biology

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“…The SRE from the c-fos promoter has been shown to be the point of integration of MAPK signaling pathways (47)(48)(49)(50)(51). The Ras-Raf-MEK-ERK signaling pathway activates transcription factors Elk-1 and Sap-1a, which bind to the SRE of the c-fos promoter (47-51, 52-61).…”

Section: Discussionmentioning

confidence: 99%

Constitutively Active Mutants of the α1a- and the α1b-Adrenergic Receptor Subtypes Reveal Coupling to Different Signaling Pathways and Physiological Responses in Rat Cardiac Myocytes

McWhinney¹,

Wenham²,

Kanwal³

et al. 2000

Journal of Biological Chemistry

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Activation of ␣ 1 -adrenergic receptors influences both the contractile activity and the growth potential of cardiac myocytes. However, the signaling pathways linking activation of specific ␣ 1 -adrenergic receptor (AR) subtypes to these physiological responses remain controversial. In the present study, a molecular approach was used to identify conclusively the signaling pathways activated in response to the individual ␣ 1A -and ␣ 1B -AR subtypes in cardiac myocytes. For this purpose, a mutant ␣ 1a -AR subtype (␣ 1a -S 290/293 -AR) was constructed based on analogy to the previously described constitutively active mutant ␣ 1b -AR subtype (␣ 1b -S 288 -294 -AR). The mutant ␣ 1a -S 290/293 -AR subtype displayed constitutive activity based on four criteria. To introduce the constitutively active ␣ 1 -AR subtypes into cardiac myocytes, recombinant Sindbis viruses encoding either the ␣ 1a -S 290/293 -AR or ␣ 1b -S 288 -294 -AR subtype were used to infect the whole cell population with >90% efficiency, thereby allowing the biochemical activities of the various signaling pathways to be measured. When expressed at comparable levels, the ␣ 1a -S 290/293 -AR subtype exhibited a significantly elevated basal level as well as agonist-stimulated level of inositol phosphate accumulation, coincident with activation of atrial natriuretic factor-luciferase gene expression. By contrast, the ␣ 1b -S 288 -294 -AR subtype displayed a markedly increased serum response element-luciferase gene expression but no activation of atrial natriuretic factor-luciferase gene expression. Taken together, this study provides the first molecular evidence for coupling of the ␣ 1a -AR and the ␣ 1b -AR subtypes to different signaling pathways in cardiac myocytes.Activation of ␣ 1 -adrenergic receptors (AR) 1 influences both the contractile activity and the growth potential of cardiac myocytes. However, despite intense investigation, the signaling pathways linking activation of specific ␣ 1 -AR subtypes to these particular physiological responses remain controversial (1). The situation is complicated by the diversity of ␣ 1 -AR subtypes. Three distinct ␣ 1 -AR subtypes have been identified by molecular cloning (2-4). Recently, the relationships between the cloned and native ␣ 1 -AR subtypes have been established by comparison of their affinity constants for a wide variety of ␣ 1 -AR subtype-selective antagonists (5, 6). From this comparison, it has been suggested that the cloned ␣ 1b -AR represents the native ␣ 1B -AR subtype; the cloned ␣ 1a/c -AR 2 corresponds to the native ␣ 1A -AR subtype; and the cloned ␣ 1d -AR is considered to represent a novel ␣ 1D -AR subtype. With the recognition that multiple ␣ 1 -AR subtypes exist, the roles of the individual ␣ 1 -AR subtypes in mediating specific physiological effects need to be investigated further.The assignment of particular physiological responses and signaling pathways first requires the elucidation of the specific ␣ 1 -ARs subtypes present in cardiac myocytes. In a previous study, we showed that all t...

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“…The promoter for c-fos contains binding sites for Stat3 and Elk-1. 55 LPS-activated Stat3 and HGFactivated Elk-1 might synergistically activate transcription of c-Fos or other AP-1 components. Such a role for Stat3 in augmenting AP-1 levels in the liver was proposed initially by Cressman et al 22 Although LPS resulted in a modest reduction in MAPK levels in response to HGF and might therefore reduce the levels of phosphorylated Elk-1, the strong activation of Stat3 by LPS might be a more important factor in augmenting AP-1.…”

Section: Lps-induced Stat3 May Function To Increase Ap-1-dna Bindingmentioning

confidence: 98%

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

et al. 1999

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The liver regenerates by replication of differentiated hepatocytes after damage or removal of part of the liver. Although several growth factors and signaling pathways are activated during regeneration, it is unclear as to which of these are essential for hepatocyte replication. We show here that low-(1 mg/kg) and high-(10 mg/kg) dose hepatocyte growth factor (HGF) induced replication of 2.1% and 11.1% of hepatocytes in rats, respectively. Lipopolysaccharide The normal liver has a remarkable ability to replicate in response to injury or partial hepatectomy (PH). A better understanding of the molecular mechanisms responsible for this process might enable liver regeneration to be induced in liver insufficiency states such as cirrhosis. In addition, this information might facilitate gene therapy, as some vectors only transduce dividing cells, and hepatocytes are normally quiescent. 1

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Synergistic increase in c-fos expression by simultaneous activation of the ras/raf/map kinase- and protein kinase A signaling pathways is mediated by the c-fos AP-1 and SRE sites

Cited by 23 publications

References 66 publications

Role of the Cyclic AMP Response Element Binding Complex and Activation of Mitogen-Activated Protein Kinases in Synergistic Activation of the Glycoprotein Hormone α Subunit Gene by Epidermal Growth Factor and Forskolin

Role of the Cyclic AMP Response Element Binding Complex and Activation of Mitogen-Activated Protein Kinases in Synergistic Activation of the Glycoprotein Hormone α Subunit Gene by Epidermal Growth Factor and Forskolin

Constitutively Active Mutants of the α1a- and the α1b-Adrenergic Receptor Subtypes Reveal Coupling to Different Signaling Pathways and Physiological Responses in Rat Cardiac Myocytes

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

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