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

Fuentes, Lida Q.; Reyes, Carlos; Sarmiento, José; Villanueva, Carolina I.; Figueroa, Carlos D.; Navarro, Javier; González, Carlos B.

doi:10.1016/j.cellsig.2008.05.009

Cited by 12 publications

(7 citation statements)

References 63 publications

(59 reference statements)

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“…This builds on a recent study with HaCaT cells showing the metalloproteinase inhibitor TAPI-2 inhibits sodium lauryl sulfate (SLS)-induced Egr-1 expression [44] . A previous study examined the link between MMP and Egr-1 expression in A-10 cells responding to the peptide hormone, arginine vasopressin [45] . However treatment with the pan-MMP inhibitor GM6001+ in that study did not inhibit Egr-1 expression but blocked induction of another immediate early gene c-Fos.…”

Section: Discussionmentioning

confidence: 99%

IL-1beta Signals through the EGF Receptor and Activates Egr-1 through MMP-ADAM

et al. 2012

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The immediate-early gene Egr-1 controls the inducible expression of many genes implicated in the pathogenesis of a range of vascular disorders, yet our understanding of the mechanisms controlling the rapid expression of this prototypic zinc finger transcription factor is poor. Here we show that Egr-1 expression induced by IL-1beta is dependent on metalloproteinases (MMP) and a disintegrin and a metalloproteinase (ADAM). Pharmacologic MMP/ADAM inhibitors and siRNA knockdown prevent IL-1beta induction of Egr-1. Further, IL-1beta activates Egr-1 via the epidermal growth factor receptor (EGFR). This is blocked by EGFR tyrosine kinase inhibition and EGFR knockdown. IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs) deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. This study reports for the first time that Egr-1 induction by IL-1beta involves EGFR and MMP/ADAM-dependent EGFR phosphorylation.

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Section: Discussionmentioning

confidence: 99%

IL-1beta Signals through the EGF Receptor and Activates Egr-1 through MMP-ADAM

et al. 2012

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“…To date, a limited number of GPCRs have been shown to interact (directly or indirectly) with EGFR. Recently, it was discovered that the vasopressin 1A receptor, a G q –coupled receptor also interacts with EGFR by co-immunoprecipitation studies, although how this interaction affects signaling of either receptor is unknown [51] . The β1-adrenergic receptor has been shown to interact with EGFR by co-immunoprecipitation and FRET analysis under basal conditions [52] .…”

Section: Discussionmentioning

confidence: 99%

GPR54 (KISS1R) Transactivates EGFR to Promote Breast Cancer Cell Invasiveness

et al. 2011

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Kisspeptins (Kp), peptide products of the Kisspeptin-1 (KISS1) gene are endogenous ligands for a G protein-coupled receptor 54 (GPR54). Previous findings have shown that KISS1 acts as a metastasis suppressor in numerous cancers in humans. However, recent studies have demonstrated that an increase in KISS1 and GPR54 expression in human breast tumors correlates with higher tumor grade and metastatic potential. At present, whether or not Kp signaling promotes breast cancer cell invasiveness, required for metastasis and the underlying mechanisms, is unknown. We have found that kisspeptin-10 (Kp-10), the most potent Kp, stimulates the invasion of human breast cancer MDA-MB-231 and Hs578T cells using Matrigel-coated Transwell chamber assays and induces the formation of invasive stellate structures in three-dimensional invasion assays. Furthermore, Kp-10 stimulated an increase in matrix metalloprotease (MMP)-9 activity. We also found that Kp-10 induced the transactivation of epidermal growth factor receptor (EGFR). Knockdown of the GPCR scaffolding protein, β-arrestin 2, inhibited Kp-10-induced EGFR transactivation as well as Kp-10 induced invasion of breast cancer cells via modulation of MMP-9 secretion and activity. Finally, we found that the two receptors associate with each other under basal conditions, and FRET analysis revealed that GPR54 interacts directly with EGFR. The stability of the receptor complex formation was increased upon treatment of cells by Kp-10. Taken together, our findings suggest a novel mechanism by which Kp signaling via GPR54 stimulates breast cancer cell invasiveness.

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“…β-Arrestins may be involved in agonist-induced MMP-mediated EGFR transactivation and cell proliferation (19). We assessed if the basal, serum-independent proliferation triggered by 247R is β-arrestin-dependent.…”

Section: R-triggered Egfr Transactivation Mediated By Enhanced Shementioning

confidence: 99%

Constitutive coupling of a naturally occurring human alpha1a-adrenergic receptor genetic variant to EGFR transactivation pathway

Oganesian

Yarov‐Yarovoy

Parks³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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We previously identified a naturally occurring human SNP, G247R, in the third intracellular loop of the α 1a -adrenergic receptor (α 1a -247R) and demonstrated that constitutive expression of α 1a -247R results in twofold increased cell proliferation compared with WT. In the present study we elucidate molecular mechanisms and signal transduction pathways responsible for increased cell proliferation unique to α 1a -247R, but not α 1a -WT, α 1b , or α 1d AR subtypes. We show that elevated levels of matrix metalloproteinase-7 (MMP7) and a disintegrin and metalloproteinase-12 (ADAM12) in α 1a -247R-expressing cells are responsible for EGF receptor (EGFR) transactivation, downstream ERK activation, and increased cell proliferation; this pathway is confirmed using MMP, EGFR, and ERK inhibitors. We demonstrate that EGFR transactivation and downstream ERK activation depends on increased shedding of heparin-binding EGF. Finally, we demonstrate that knockdown of MMP7 or β-arrestin1 by shRNAs results in attenuation of proliferation of cells expressing α 1a -247R. Importantly, accelerated cell proliferation triggered by the α 1a -247R is serum-and agonist-independent, providing unique evidence for constitutive active coupling to the β-arrestin1/MMP/EGFR transactivation pathway by any G protein-coupled receptor. These findings raise the possibility of a previously unexplored mechanism for sympathetically mediated human hypertension triggered by a naturally occurring human genetic variant.

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

Cited by 12 publications

References 63 publications

IL-1beta Signals through the EGF Receptor and Activates Egr-1 through MMP-ADAM

IL-1beta Signals through the EGF Receptor and Activates Egr-1 through MMP-ADAM

GPR54 (KISS1R) Transactivates EGFR to Promote Breast Cancer Cell Invasiveness

Constitutive coupling of a naturally occurring human alpha1a-adrenergic receptor genetic variant to EGFR transactivation pathway

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