Histamine stimulation of MMP-1(collagenase-1) secretion and gene expression in gastric epithelial cells: Role of EGFR transactivation and the MAP kinase pathway

Extracellular zinc promotes cell proliferation and its deficiency leads to impairment of this process, which is particularly important in epithelial cells. We have recently characterized a zinc-sensing receptor (ZnR) linking extracellular zinc to intracellular release of calcium. In the present study, we addressed the role of extracellular zinc, acting via the ZnR, in regulating the MAP kinase pathway and Na+/H+exchange in colonocytes. We demonstrate that Ca2+release, mediated by the ZnR, induces phosphorylation of ERK1/2, which is highly metal-specific, mediated by physiological concentrations of extracellular Zn2+but not by Cd2+, Fe2+, Ni2+, or Mn2+. Desensitization of the ZnR by Zn2+, is followed by ∼90% inhibition of the Zn2+-dependent ERK1/2 phosphorylation, indicating that the ZnR is a principal link between extracellular Zn2+and ERK1/2 activation. Application of both the IP3pathway and PI 3-kinase antagonists largely inhibited Zn2+-dependent ERK1/2 phosphorylation. The physiological significance of the Zn2+-dependent activation of ERK1/2 was addressed by monitoring Na+/H+exchanger activity in HT29 cells and in native colon epithelium. Preincubation of the cells with zinc was followed by robust activation of Na+/H+exchange, which was eliminated by cariporide (0.5 μm); indicating that zinc enhances the activity of NHE1. Activation of NHE1 by zinc was totally blocked by the ERK1/2 inhibitor, U0126. Prolonged acidification, in contrast, stimulates NHE1 by a distinct pathway that is not affected by extracellular Zn2+or inhibitors of the MAP kinase pathway. Desensitization of ZnR activity eliminates the Zn2+-dependent, but not the prolonged acidification-dependent activation of NHE1, indicating that Zn2+-dependent activation of H+extrusion is specifically mediated by the ZnR. Our results support a role for extracellular zinc, acting through the ZnR, in regulating multiple signaling pathways that affect pH homeostasis in colonocytes. Furthermore activation of both, ERK and NHE1, by extracellular zinc may provide the mechanism linking zinc to enhanced cell proliferation.

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MAP Kinase Pathway is Involved in IGF-1-Stimulated Proliferation of Human Retinal Pigment Epithelial Cells (hRPE)

Current Eye Research ◽

10.3109/02713680903177890 ◽

2009 ◽

Vol 34 (10) ◽

pp. 867-876 ◽

Cited By ~ 19

Author(s):

Christina Y. Weng ◽

Piyush C. Kothary ◽

Angela J. Verkade ◽

David M. Reed ◽

Monte A. Del Monte

Keyword(s):

Epithelial Cells ◽

Map Kinase ◽

Retinal Pigment Epithelial ◽

Retinal Pigment ◽

Retinal Pigment Epithelial Cells ◽

Pigment Epithelial ◽

Map Kinase Pathway ◽

Kinase Pathway ◽

Pigment Epithelial Cells

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The K5 Capsule of Escherichia coli Strain Nissle 1917 Is Important in Stimulating Expression of Toll-Like Receptor 5, CD14, MyD88, and TRIF Together with the Induction of Interleukin-8 Expression via the Mitogen-Activated Protein Kinase Pathway in Epithelial Cells

Infection and Immunity ◽

10.1128/iai.01406-09 ◽

2010 ◽

Vol 78 (5) ◽

pp. 2153-2162 ◽

Cited By ~ 26

Author(s):

Mohamed Hafez ◽

Kelly Hayes ◽

Marie Goldrick ◽

Richard K. Grencis ◽

Ian S. Roberts

Keyword(s):

Escherichia Coli ◽

Epithelial Cells ◽

Map Kinase ◽

Interleukin 8 ◽

Mitogen Activated Protein Kinase ◽

Probiotic Properties ◽

Toll Like Receptor ◽

Mitogen Activated Protein ◽

Map Kinase Pathway ◽

Kinase Pathway

ABSTRACT Escherichia coli strain Nissle 1917, which has been widely used as a probiotic for the treatment of inflammatory bowel disorders, expresses a K5 capsule, the expression of which is often associated with extraintestinal and urinary tract isolates of E. coli. Previously, it had been shown that the expression of a K5 capsule by Nissle 1917 was important in mediating interactions with epithelial cells and the extent of chemokine expression. In this paper, we show that infection with Nissle 1917 induces expression of Toll-like receptor 4 (TLR4) and TLR5 in Caco-2 cells and that maximal induction of TLR5 required the K5 capsule. In addition, purified K5 polysaccharide was capable of inducing expression of TLR5 and mCD14 and potentiated the activity of both TLR4 and TLR5 agonists to increase the proinflammatory response. Infection with Nissle 1917 also increased the expression of the adaptor molecules MyD88 and TRIF, which was K5 capsule dependent. By Western blot analysis, it was possible to show that induction of interleukin-8 by Nissle 1917 was predominantly through the mitogen-activated protein (MAP) kinase pathway and that expression of the K5 capsule was important for activation of the MAP kinase pathway. This paper provides new information on the function of the K5 capsule in mediating interactions between Nissle 1917 and epithelial cells and the mechanisms that underlie the probiotic properties of Nissle 1917.

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The Role of Translational Medicine in Optimization of Therapies Targeting the RAS-MAP Kinase Pathway

Targeted Therapy of Acute Myeloid Leukemia ◽

10.1007/978-1-4939-1393-0_15 ◽

2014 ◽

pp. 307-324

Author(s):

Judith S. Sebolt-Leopold

Keyword(s):

Map Kinase ◽

Translational Medicine ◽

Map Kinase Pathway ◽

Kinase Pathway

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Characterization of factor-independent variants derived from TF-1 hematopoietic progenitor cells: the role of the Raf/MAP kinase pathway in the anti-apoptotic effect of GM-CSF

Oncogene ◽

10.1038/sj.onc.1200884 ◽

1997 ◽

Vol 14 (6) ◽

pp. 721-728 ◽

Cited By ~ 12

Author(s):

Jhy-Rong Chao ◽

Chyi-Shyan Chen ◽

Ting-Fang Wang ◽

Li-Hui Tseng ◽

Jaw-Ji Tsai ◽

...

Keyword(s):

Map Kinase ◽

Progenitor Cells ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Gm Csf ◽

Apoptotic Effect ◽

Map Kinase Pathway ◽

Kinase Pathway

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Differential regulation of Raf-1 and B-Raf and Ras-dependent activation of mitogen-activated protein kinase by cyclic AMP in PC12 cells.

Molecular and Cellular Biology ◽

10.1128/mcb.15.10.5524 ◽

1995 ◽

Vol 15 (10) ◽

pp. 5524-5530 ◽

Cited By ~ 102

Author(s):

P Erhardt ◽

J Troppmair ◽

U R Rapp ◽

G M Cooper

Keyword(s):

Growth Factor ◽

Cyclic Amp ◽

Map Kinase ◽

Pc12 Cells ◽

Dominant Negative ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Map Kinase Pathway ◽

Kinase Pathway ◽

Stimulation Of

Growth factor stimulation of the mitogen-activated protein (MAP) kinase pathway in fibroblasts is inhibited by cyclic AMP (cAMP) as a result of inhibition of Raf-1. In contrast, cAMP inhibits neither nerve growth factor-induced MAP kinase activation nor differentiation in PC12 pheochromocytoma cells. Instead, in PC12 cells cAMP activates MAP kinase. Since one of the major differences between the Ras/Raf/MAP kinase cascades of these cell types is the expression of B-Raf in PC12 cells, we compared the effects of cAMP on Raf-1 and B-Raf. In PC12 cells maintained in serum-containing medium, B-Raf was refractory to inhibition by cAMP, whereas Raf-1 was effectively inhibited. In contrast, both B-Raf and Raf-1 were inhibited by cAMP in serum-starved PC12 cells. The effect of cAMP is thus dependent upon growth conditions, with B-Raf being resistant to cAMP inhibition in the presence of serum. These results were extended by studies of Rat-1 fibroblasts into which B-Raf had been introduced by transfection. As in PC12 cells, B-Raf was resistant to inhibition by cAMP in the presence of serum, whereas Raf-1 was effectively inhibited. In addition, the expression of B-Raf rendered Rat-1 cells resistant to the inhibitory effects of cAMP on both growth factor-induced activation of MAP kinase and mitogenesis. These results indicate that Raf-1 and B-Raf are differentially sensitive to inhibition by cAMP and that B-Raf expression can contribute to cell type-specific differences in the regulation of the MAP kinase pathway. In contrast to the situation in PC12 cells, cAMP by itself did not stimulate MAP kinase in B-Raf-expressing Rat-1 cells. The activation of MAP kinase by cAMP in PC12 cells was inhibited by the expression of a dominant negative Ras mutant, indicating that cAMP acts on a target upstream of Ras. Thus, it appears that a signaling component upstream of Ras is also require for cAMP stimulation of MAP kinase in PC12 cells.

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