S-Nitrosylation of the epidermal growth factor receptor: A regulatory mechanism of receptor tyrosine kinase activity

Murillo‐Carretero, Maribel; Torroglosa, Ana; Castro, Carmen; Villalobo, Antonio; Estrada, Carmen

doi:10.1016/j.freeradbiomed.2008.10.048

Cited by 48 publications

(46 citation statements)

References 56 publications

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“…The treatment that we propose is the dual inhibition of MAPK and PI3K pathways. NO inhibits IGF-IR and EGFR activity, as reported previously (29,30). Furthermore, NO induces the degradation of IRS-1 protein and the phosphorylation of IRS-1 (14,29,30).…”

Section: Discussionsupporting

confidence: 76%

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NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells

Furuhashi

Sugita

Horino³

et al. 2011

Int J Oncol

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Abstract.Nitric oxide (NO) shows tumoricidal activity. We had previously reported that NO downregulates the phosphatidylinositol-3-kinase/Akt pathway, but upregulates the MEK/ERK pathway downstream of growth factor signaling. We hypothesized that NO donor and MEK inhibitor in combination synergistically inhibit the viability of cancer cells compared to either NO donor or MEK inhibitor alone. We determined the effects of S-nitrosoglutathione (GSNO, NO-donor) and U0126 (MEK inhibitor) on insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) signaling, proliferation and invasion in cancer cell lines. GSNO inhibits phosphorylation of IGF-I receptor (IGF-IR), EGF receptor (EGFR) and Akt, but upregulates ERK1/2 phosphorylation in MIAPaCa-2 and HCT-116 cells after stimulation by IGF-I and EGF. On the other hand, U0126 inhibits phosphorylation of ERK1/2, but upregulates phosphorylation of IGF-IR and EGFR in MIAPaCa-2 and HCT-116 cells. The combination of GSNO and U0126 downregulates phosphorylation of IGF-IR, EGFR, Akt and ERK1/2 after stimulation by IGF-I and EGF. GSNO as well as U0126, inhibits the proliferation of MIAPaCa-2, HCT-116, Panc-1, MCF-7, HT-29 and AGS cells in a dose-dependent manner. GSNO and U0126 in combination synergistically inhibit proliferation and invasion of cancer cells. These results indicate that the combined treatment of NO donor and MEK inhibitor may be promising in cancer therapy.

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Section: Discussionsupporting

confidence: 76%

“…NO inhibits IGF-IR and EGFR activity, as reported previously (29,30). Furthermore, NO induces the degradation of IRS-1 protein and the phosphorylation of IRS-1 (14,29,30). In addition, Yasukawa et al reported that NO directly modifies Akt protein and inhibits its activity (11).…”

Section: Discussionmentioning

confidence: 54%

NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells

Furuhashi

Sugita

Horino³

et al. 2011

Int J Oncol

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“…Activation of the p21Ras -ERK1/2 MAP kinases signaling pathway was correlated with: Ras S-nitrosylation; activation of the EGF-R stimulated by the ERK1/2 MAP kinases; promotion of cell cycle progression and stimulation of cell proliferation [19][20][21][22][23]. Conversely, others have shown an inhibitory action of NO over EGF-R mediated tyrosine phosphorylation signaling events [24]. Therefore, the molecular mechanism by which NO modulates EGF-R tyrosine phosphorylation and the physiological consequences on cell signaling is still a focal point of controversies.…”

Section: Introductionmentioning

confidence: 99%

Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth factor receptor-mediated signaling pathway in bradykinin-stimulated angiogenesis

Moraes

Costa

Batista

et al. 2014

Archives of Biochemistry and Biophysics

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“…In isolated neural stem cells from the SVZ, supraphysiological concentrations of NO inhibit neural stem cell proliferation and promote differentiation of precursors into astrocytes [11,12]. Torroglosa et al have suggested that NO modulates the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) [11], by a mechanism involving nitrosylation of specific cysteine residues in the EGFR [13]. On the other hand, NO was found to increase Author contributions: B.P.C.…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Stimulates the Proliferation of Neural Stem Cells Bypassing the Epidermal Growth Factor Receptor

et al. 2010

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Nitric oxide (NO) was described to inhibit the proliferation of neural stem cells. Some evidence suggests that NO, under certain conditions, can also promote cell proliferation, although the mechanisms responsible for a potential proliferative effect of NO in neural stem cells have remained unaddressed. In this work, we investigated and characterized the proliferative effect of NO in cell cultures obtained from the mouse subventricular zone. We found that the NO donor NOC-18 (10 lM) increased cell proliferation, whereas higher concentrations (100 lM) inhibited cell proliferation. Increased cell proliferation was detected rapidly following exposure to NO and was prevented by blocking the mitogen-activated kinase (MAPK) pathway, independently of the epidermal growth factor (EGF) receptor. Downstream of the EGF receptor, NO activated p21Ras and the MAPK pathway, resulting in a decrease in the nuclear presence of the cyclin-dependent kinase inhibitor 1, p27 KIP1 , allowing for cell cycle progression. Furthermore, in a mouse model that shows increased proliferation of neural stem cells in the hippocampus following seizure injury, we observed that the absence of inducible nitric oxide synthase (iNOS 2/2 mice) prevented the increase in cell proliferation observed following seizures in wild-type mice, showing that NO from iNOS origin is important for increased cell proliferation following a brain insult. Overall, we show that NO is able to stimulate the proliferation of neural stem cells bypassing the EGF receptor and promoting cell division. Moreover, under pathophysiological conditions in vivo, NO from iNOS origin also promotes proliferation in the hippocampus. STEM CELLS

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S-Nitrosylation of the epidermal growth factor receptor: A regulatory mechanism of receptor tyrosine kinase activity

Cited by 48 publications

References 56 publications

NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells

NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells

Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth factor receptor-mediated signaling pathway in bradykinin-stimulated angiogenesis

Nitric Oxide Stimulates the Proliferation of Neural Stem Cells Bypassing the Epidermal Growth Factor Receptor

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