GPCR-mediated transactivation of RTKs in the CNS: mechanisms and consequences

Shah, Bukhtiar H.; Catt, Kevin J.

doi:10.1016/j.tins.2003.11.003

Cited by 125 publications

(82 citation statements)

References 65 publications

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“…There are many examples of crosstalk between G-protein-coupled receptors (GPCRs) and RTKs (reviewed by Shah & Catt 2004, Waters et al 2004. One group of GPCRs that interact with RTKs are the S1P receptors (e.g.…”

Section: Discussionmentioning

confidence: 99%

Interactions between sphingosine-1-phosphate and vascular endothelial growth factor signalling in ML-1 follicular thyroid carcinoma cells

Balthasar¹,

Bergelin²,

Löf³

et al. 2008

Endocrine Related Cancer

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Sphingosine-1-phosphate (S1P) induces migration of human ML-1 thyroid follicular cancer cells and inhibits migration of human FRO anaplastic thyroid cancer cells. As tumour cells often secrete vascular endothelial growth factor (VEGF), we investigated a possible interaction between S1P and VEGF signalling in the regulation of thyroid tumour cell migration. We found that both ML-1 and FRO cells secreted VEGF-A (w3.6 and !0

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Section: Discussionmentioning

confidence: 99%

Interactions between sphingosine-1-phosphate and vascular endothelial growth factor signalling in ML-1 follicular thyroid carcinoma cells

Balthasar¹,

Bergelin²,

Löf³

et al. 2008

Endocrine Related Cancer

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“…GPCRs are plasma membrane-localized glycoprotein receptors that couple to heterotrimeric guanine nucleotide-binding proteins (G proteins) and are the largest family (superfamily) of receptors that regulate cells (Fichter et al, 2010). Many of the growth-promoting effects of GPCR stimulation are mediated through the activation of receptor tyrosine kinases such as EGFR (Wetzker and Bohmer, 2003;Shah and Catt, 2004).…”

Section: Mirna Profiling In Mutated Kras Versus Wildtype Krasmentioning

confidence: 99%

MicroRNA profiling differentiates colorectal cancer according to KRAS status

Mosakhani

Sarhadi

Borze

et al. 2011

Genes Chromosomes & Cancer

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Recent studies have shown the important role of microRNAs (miRNAs) in a variety of biological processes, and in its ability to distinguish tumors according to their prognostic and predictive properties. To identify miRNA signatures associated with colorectal carcinoma (CRC) and with KRAS status, we studied, using Agilent's miRNA microarrays, miRNA expression in primary tumors from 55 metastatic CRC patients, including 15 with mutant and 40 with wild-type KRAS. Comparing these with normal colon tissue, we identified 49 miRNAs-including 19 novel miRNAs-significantly deregulated in tumor tissue. The presence of the KRAS mutation was associated with up-regulation of miR-127-3p, miR-92a, and miR-486-3p and down-regulation of miR-378. Increased expression of miR-127-3p and miR-92a in KRAS mutant tumors was significantly confirmed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) (P < 0.05). We identified some predicted target genes of differentially expressed miRNAs between mutated and wild-type KRAS, such as RSG3 and TOB1, which are involved in apoptosis and proliferation. Target prediction and pathway analysis suggest a possible role for deregulated miRNAs in nicotinamide adenine dinucleotide phosphate (NADPH) regeneration and G protein-coupled receptor signaling pathways.

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“…Several receptor tyrosine kinases (RTKs) activate both the Akt and ERK1/2 signaling pathways. Many G protein-coupled receptors (GPCRs) transactivate RTKs, resulting in Akt and ERK1/2 activation, which results in cell protection and survival [16] . Epidermal growth factor receptor (EGFR) is a typical RTK expressed in the membrane of many kinds of cells.…”

Section: Introductionmentioning

confidence: 99%

Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

Zhong

Song

et al. 2015

Acta Pharmacol Sin

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Aim: Paeoniflorin from Chinese herb Paeoniae Radix has been shown to ameliorate middle cerebral artery occlusion-induced ischemia in rats. The aim of this study was to investigate the mechanisms underlying the neuroprotective action of PF in cultured rat cortical neurons. Methods: Primary cultured cortical neurons of rats were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) insult. Cell survival was determined using MTT assay. HEK293 cells stably transfected with A 1 R (HEK293/A 1 R) were used for detailed analysis. Phosphorylation of the signaling proteins was evaluated by Western blot or immunoprecipitation. Receptor interactions were identified using co-immunoprecipitation and immunofluorescence staining. Results: Paeoniflorin (10 nmol/L to 1 μmol/L) increased the survival of neurons subjected to OGD/R. Furthermore, paeoniflorin increased the phosphorylation of Akt and ERK1/2 in these neurons. These effects were blocked by PI3K inhibitor wortmannin or MEK inhibitor U0126. Paeoniflorin also increased the phosphorylation of Akt and ERK1/2 in HEK293/A 1 R cells. Both A 1 R antagonist DPCPX and EGFR inhibitor AG1478 not only blocked paeoniflorin-induced phosphorylation of ERK1/2 and Akt in HEK293/A 1 R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. In addition, paeoniflorin increased the phosphorylation of Src kinase and activation of MMP-2 in HEK293/A 1 R cells. Both Src inhibitor PP2 and MMP-2/MMP-9 inhibitor BiPs not only blocked paeoniflorininduced phosphorylation of ERK1/2 (and Akt) in HEK293/A 1 R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. Conclusion: Paeoniflorin promotes the survival of cultured cortical neurons by increasing Akt and ERK1/2 phosphorylation via A 1 Rmediated transactivation of EGFR.

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GPCR-mediated transactivation of RTKs in the CNS: mechanisms and consequences

Cited by 125 publications

References 65 publications

Interactions between sphingosine-1-phosphate and vascular endothelial growth factor signalling in ML-1 follicular thyroid carcinoma cells

Interactions between sphingosine-1-phosphate and vascular endothelial growth factor signalling in ML-1 follicular thyroid carcinoma cells

MicroRNA profiling differentiates colorectal cancer according to KRAS status

Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

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