Epidermal-growth-factor receptor and metalloproteinases mediate thromboxane A2-dependent extracellular-signal-regulated kinase activation

Gallet, Carole; Blaie, Stéphanie; Lévy-Toledano, S; Habib, Aı̈da

doi:10.1042/bj20021030

Cited by 21 publications

(16 citation statements)

References 60 publications

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“…We have demonstrated that I-BOP induced rapid activation of ERK primarily through EGFR pathway since EGFR inhibitor blocked phosphorylation almost totally. TP-mediated transactivation of EGFR in eventual activation of ERK has also been reported in several cell lines [8][9][10]. In addition to EGFR, other signaling pathway such as activation of PKC was shown to involve in ERK activation in these cell lines although we did not see PKC being involved in a significant way in A549 cells.…”

Section: Discussionsupporting

confidence: 40%

“…ERK phosphorylation mediated by TP activation was extensively studied by several groups [8][9][10]. We have demonstrated that I-BOP induced rapid activation of ERK primarily through EGFR pathway since EGFR inhibitor blocked phosphorylation almost totally.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of TPα also leads to stimulation of adenylate cyclase generating cyclic AMP which activates protein kinase A (PKA), whereas activation of TPβ results in inhibition of adenylate cyclase [7]. Activation of TPs also initiates signaling cascades leading to activation of various kinases known to be involved in mitogenic responses, such as epidermal growth factor receptor (EGFR) [8], extracellular signal-regulated kinase (ERK) [9], Akt/protein kinase B (PKB) [10] and glycogen synthase kinase (GSK) [11]. Apparently, TP signaling is very much related to mitogenesis of target cells.…”

Section: Introductionmentioning

confidence: 99%

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Activation of thromboxane receptor α induces expression of cyclooxygenase-2 through multiple signaling pathways in A549 human lung adenocarcinoma cells

Wei

Yan

et al. 2007

Biochemical Pharmacology

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Human lung adenocarcinoma A549 cells stably transfected with TPα (A549-TPα) were used to study agonist I-BOP-induced expression of cyclooxygenase-2 (COX-2) and the related mechanisms of induced expression. I-BOP, a TP agonist, induced a time and dose dependent expression of COX-2 in A549-TPα cells as revealed by Western blot and by the synthesis of PGE 2 and TXB 2 which was totally inhibited by COX-2 inhibitors. The signaling pathways of I-BOP-induced COX-2 expression were elucidated by using various inhibitors of the signaling molecules. The effects of these inhibitors were assessed at three different levels of COX-2 expression: protein, enzyme activity and promoter activity. Within MAPK family, both ERK and p38 MAPK but not JNK/SAPK pathways were involved in the induction. Other pathways such as JAK/Stat3 pathway and β-catenin/TCF/LEF pathway also participated in the induction. The activation of key signaling molecules, ERK, p38 MAPK, CREB and NF-κB, involved in the COX-2 transcription was further studied at the phosphorylation step. Activation of ERK and p38 MAPK appeared to be mediated primarily by transactivation of EGFR, whereas activation of CREB and NF-κB was mediated by PKA, PKC and ERK. The role of CREB and NF-κB in I-BOP-induced COX-2 expression was further explored at the COX-2 promoter level. Studies on promoter fragments of different length and mutation of responsive motifs indicated that CRE and NF-κB sites are critical for the COX-2 induction. Distal NF-κB site is essential for the basal induction of the COX-2 transcription, whereas CRE and proximal NF-κB sites are important for the induced transcription. These results indicate that I-BOP induced COX-2 expression through multiple signaling pathways leading to the activation of CREB and NF-κB transcriptional factors and subsequent COX-2 transcription.

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Section: Discussionsupporting

confidence: 40%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of thromboxane receptor α induces expression of cyclooxygenase-2 through multiple signaling pathways in A549 human lung adenocarcinoma cells

Wei

Yan

et al. 2007

Biochemical Pharmacology

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“…The mechanism of GPCR-mediated metalloprotease activation is not fully understood, and several signaling molecules have been implicated in this process in various cell types (6,8,25,26). We have recently shown that both Src and Pyk2 have important roles in GnRH-induced ERK1/2 activation in GT1-7 cells (11).…”

Section: Fig 3 Hb-egf Production Through Metalloprotease Activationmentioning

confidence: 99%

Neuropeptide-induced Transactivation of a Neuronal Epidermal Growth Factor Receptor Is Mediated by Metalloprotease-dependent Formation of Heparin-binding Epidermal Growth Factor

Shah

Farshori

Catt

2004

Journal of Biological Chemistry

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Numerous external stimuli, including G protein-coupled receptor agonists, cytokines, growth factors, and steroids activate mitogen-activated protein kinases (MAPKs) through phosphorylation of the epidermal growth factor receptor (EGF-R). In immortalized hypothalamic neurons (GT1-7 cells), agonist binding to the gonadotropin-releasing hormone receptor (GnRH-R) causes phosphorylation of MAPKs that is mediated by protein kinase C (PKC)-dependent transactivation of the EGF-R. An analysis of the mechanisms involved in this process showed that GnRH stimulation of GT1-7 cells causes release/shedding of the soluble ligand, heparin binding epidermal growth factor (HB-EGF), as a consequence of metalloprotease activation. GnRH-induced phosphorylation of the EGF-R and, subsequently, of Shc, ERK1/2, and its dependent protein, p90 RSK-1 (p90 ribosomal S6 kinase 1 or RSK-1), was abolished by metalloprotease inhibition. Similarly, blockade of the effect of HB-EGF with the selective inhibitor CRM197 or a neutralizing antibody attenuated signals generated by GnRH and phorbol 12-myristate 13-acetate, but not those stimulated by EGF. In contrast, phosphorylation of the EGF-R, Shc, and ERK1/2 by EGF and HB-EGF was independent of PKC and metalloprotease activity. The signaling characteristics of HB-EGF closely resembled those of GnRH and EGF in terms of the phosphorylation of EGF-R, Shc, ERK1/2, and RSK-1 as well as the nuclear translocation of RSK-1. However, neither the selective Src kinase inhibitor PP2 nor the overexpression of negative regulatory Src kinase and dominant negative Pyk2 had any effect on HB-EGF-induced responses. In contrast to GT1-7 cells, human embryonic kidney 293 cells expressing the GnRH-R did not exhibit metalloprotease induction and EGF-R transactivation during GnRH stimulation. These data indicate that the GnRH-induced transactivation of the EGF-R and the subsequent ERK1/2 phosphorylation result from ectodomain shedding of HB-EGF through PKC-dependent activation of metalloprotease(s) in neuronal GT1-7 cells.

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“…GPCRs transactivate EGFR via several mechanisms [20,21]. One mechanism involves the activation of a membrane-bound metalloproteinase that catalyzes the extracellular shedding of HB-EGF, which then actives the EGFR [22][23][24][25]. A second mechanism involves the activation of c-Src, which leads to the phosphorylation and activation of EGFR [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Vasopressin up-regulates the expression of growth-related immediate-early genes via two distinct EGF receptor transactivation pathways

Fuentes

Reyes

Sarmiento

et al. 2008

Cellular Signalling

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Activation of V 1a receptor triggers the expression of growth-related immediate-early genes (IEGs), including c-Fos and Egr-1. Here we found that pre-treatment of rat vascular smooth muscle A-10 cell line with the EGF receptor inhibitor AG1478 or the over-expression of an EGFR dominant negative mutant (HEBCD533) blocked the vasopressin-induced expression of IEGs, suggesting that activation of these early genes mediated by V 1a receptor is via transactivation of the EGF receptor. Importantly, the inhibition of the metalloproteinases, which catalyzed the shedding of the EGF receptor agonist HB-EGF, selectively blocked the vasopressin-induced expression c-Fos. On the other hand, the inhibition of c-Src selectively blocked the vasopressin-induced expression of Egr-1. Interestingly, in contrast to the expression of c-Fos, the expression of Egr-1 was mediated via the Ras/MEK/MAPK-dependent signalling pathway. Vasopressin-triggered expression of both genes required the release of intracellular calcium, activation of PKC and β-arrestin 2. These findings demonstrated that vasopressin up-regulated the expression of c-Fos and Erg-1 via transactivation of two distinct EGF receptor-dependent signalling pathways.

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Epidermal-growth-factor receptor and metalloproteinases mediate thromboxane A2-dependent extracellular-signal-regulated kinase activation

Cited by 21 publications

References 60 publications

Activation of thromboxane receptor α induces expression of cyclooxygenase-2 through multiple signaling pathways in A549 human lung adenocarcinoma cells

Activation of thromboxane receptor α induces expression of cyclooxygenase-2 through multiple signaling pathways in A549 human lung adenocarcinoma cells

Neuropeptide-induced Transactivation of a Neuronal Epidermal Growth Factor Receptor Is Mediated by Metalloprotease-dependent Formation of Heparin-binding Epidermal Growth Factor

Vasopressin up-regulates the expression of growth-related immediate-early genes via two distinct EGF receptor transactivation pathways

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