1-(Carboxymethylthio)tetradecane Attenuates PDGF- and TPA-Induced c-fosmRNA Expression and Increases the Formation of Phosphatidylethanolamine with a Shift from Less to More Polar Molecular Species in C3H/10T12 Cells

Helleland, Charlotte; Eiane, Siv A.; Berge, Rolf K.; Holmsen, Holm

doi:10.1006/excr.1997.3697

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…If this was the most prominent effect of TTA, the TPA-induced signal transduction pathway would not be affected since TPA mimics, and replaces, DAG in activating PKC directly (43). The attenuation of TPA-mediated c-fos mRNA expression in TTA-treated cells (12) argues against a DAG effect and suggests that TTA might alter lipid and/or membrane composition important for PKC mediated signal transduction downstream of DAG synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…We previously showed that TTA attenuates the expression of c-fos mRNA in response to mitogenic activators (12). As several of the early steps in cell signaling involve membrane-associated factors, we studied the mitogenmediated activation of the down-stream factor ERK in the MAPK pathway.…”

Section: Tta-treatment Of 10t1/2 Cells Does Not Effect Erk Enzyme Actmentioning

confidence: 99%

“…TTA is known to affect the expression and activity of several genes involved in lipid metabolism (5)(6)(7)(8)(9)(10)(11), and is incorporated into liver lipids and plasma lipoproteins. We have previously found that TTA increases the formation of phosphatidylethanolamine (PE) with a shift from less to more polar molecular species in fibroblasts, and that TTA attenuates PDGF-and 12-O -tetradecanoyl phorbol-13-acetate (TPA)-induced c-fos mRNA expression (12). Altogether, TTA seems to alter the lipid composition in the cells in a manner that effects the PDGF-and TPA-induced signal transduction pathway leading to the regulation of c -fos mRNA expression.…”

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confidence: 99%

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Nuclear import of factors involved in signaling is inhibited in C3H/10T1/2 cells treated with tetradecylthioacetic acid

Bjørndal

Helleland

Bøe

et al. 2002

Journal of Lipid Research

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The non-␤ -oxidisable tetradecylthioacetic acid (TTA) is incorporated into cellular membranes when C3H/ 10T1/2 cells are cultured in TTA-containing medium. We here demonstrate that this alteration in cellular membranes affect the nuclear translocation of proteins involved in signal transduction. Analysis of cellular fatty acid composition shows that TTA and TTA:1n-8 constitute approximately 40 mol% of total fatty acids in cellular/nuclear membranes. Activation of c-fos expression is significantly inhibited in TTA-treated cells but the enzymatic activation of mitogen activated protein kinase (ERK) is not affected. Immunofluorescence and confocal microscopy studies demonstrate that in mitogene-stimulated TTA-treated cells, the translocation of phosphorylated ERK1/2, protein kinase C ␣ (PKC ␣ ), and PKC ␤ 1 from the cytoplasm into the nucleus is considerably decreased and delayed. Concomitant with a decreased nuclear import, ERK1/2 dephosphorylation is decreased in TTA-treated cells. There is no TTA-induced inhibition of nuclear import of proteins with a classical nuclear localization signal (NLS), as seen by in vitro nuclear import experiments of BSA fused to the NLS from SV40 large T, or in vivo studies of hnRNP A1 nuclear import. The expression levels of Importin ␣ , Importin ␤ , Importin 7, and NTF2 are not altered in the TTA-treated cells. Taken together, our data indicate that TTA treatment causes changes in cellular fatty acid composition that negatively affect NLS-independent mechanisms of protein translocation through the nuclear pore complex. -Bjørndal, B., C. Helleland, S-O. Bøe, O. A. Gudbrandsen, K-H. Kalland, P. Bohov, R. K. Berge, and J. R. Lillehaug. Nuclear import of factors involved in signaling is inhibited in C3H/10T1/2 cells treated with tetradecylthioacetic acid.

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Section: Discussionmentioning

confidence: 99%

Section: Tta-treatment Of 10t1/2 Cells Does Not Effect Erk Enzyme Actmentioning

confidence: 99%

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confidence: 99%

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Nuclear import of factors involved in signaling is inhibited in C3H/10T1/2 cells treated with tetradecylthioacetic acid

Bjørndal

Helleland

Bøe

et al. 2002

Journal of Lipid Research

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“…31 Total RNA (20 lg) was used in Northern blot experiments. The electrophoresis, blotting and hybridization conditions were as described in Helleland et al 32 The specific activities of the DNA probes were approximately 1 3 10 9 cpm/lg DNA. RT-PCR primers were 5 0 -CCC TTT TTC TGG AGA CTA-3 0 (52°C), 5 0 -GAT CCT CCC TTT ATC CAG-3 0 (56°C) and 5 0 -CAG GTG GGG TCT TTC ATT CC-3 0 (62°C).…”

Section: Rna Purification and Analysismentioning

confidence: 99%

RACK1 regulates Ki‐Ras‐mediated signaling and morphological transformation of NIH 3T3 cells

Bjørndal

Myklebust

Rosendal

et al. 2006

Intl Journal of Cancer

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Activating Ras mutations are involved in a significant fraction of human tumors. A suppressor screen using a retroviral mouse fibroblast cDNA library was performed to identify novel factors in Ras-mediated transformation. We identified a novel potent inhibitor of Ras-mediated morphological transformation encoded by a truncated version of the receptor for activated C-kinase (RACK1). The truncated protein, designated RACK1DWD1, lacked the N-terminal 49 amino acids encoding the first of the 7 WD40 repeats in RACK1. RACK1DWD1 expression restored contact inhibition, stress fiber formation and reduced ERK phosphorylation in Ki-Ras transformed NIH 3T3 cells. We demonstrate that truncated RACK1 is involved in complexes consisting of wildtype RACK1 and protein kinase C isoforms a, bI and d, compromising the transduction of an activated Ras signal to the Raf-MEK-ERK pathway. The cellular localization of RACK1DWD1 differed from wtRACK1, indicating that signaling complexes containing the truncated version of RACK1 are incorrectly localized. Notably, 12-O-tetradecanoyl-13-phorbol acetate (TPA) mediated intracellular translocation of RACK1-interacting PKC a and d was abrogated in RACK1DWD1-expressing cells. Our data support a model where RACK1 acts as a key factor in Ki-Ras-mediated morphological transformation. ' 2006 Wiley-Liss, Inc.Key words: ERK; PKC; RACK1; Ras; transformation Members of the ras gene family (Ki-ras, Ha-ras and N-ras) are structurally related and encode proteins (p21) known to play an important role in the regulation of normal signal transduction and cell growth. A range of ras mutations are present with high frequency in different human tumors. The mechanism by which mutated Ras contributes to cancer development and morphological transformation of cells is still not completely understood. Ras generates downstream effects through Raf, Rac and Rho affecting cell growth, lamellipodia formation and stress fiber formation, respectively.1-3 Activated Ras recruits Raf-1 from the cytosol to the cell membrane, where Raf-1 activation takes place through dephosphorylation of inhibitory sites by protein phosphatase 2A (PP2A) as well as the phosphorylation of activating sites by a range of kinases. Activated Raf-1 phosphorylates and activates MEK (ERK/ MAPK kinase), which in turn phosphorylates and activates extracellular-signal-regulated kinase (ERK/MAPK). Activated ERK has many substrates in the cytosol, and in the nucleus it controls gene expression by phosphorylating transcription factors such as Elk-1 and other Ets-family proteins. [4][5][6] The activation of the ERK/ MAPK pathway is central in Ras signaling, and expression of active ERK is sufficient to transform 3T3 cells.7 Importantly, mutations in B-Raf are frequently observed in human cancers (melanomas). In addition, the c-Jun N-terminal kinase (JNK)/ MAPK pathway, 22 In an attempt to identify and characterize novel factors inhibiting the transforming signal of mutated Ki-Ras, we used a retroviral cDNA expression screen in NIH 3T3 cells. Here, we show th...

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Chlorpromazine interaction with phosphatidylserines: A 13C and 31P solid-state NMR study

Gjerde

Holmsen

Nerdal

2004

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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1-(Carboxymethylthio)tetradecane Attenuates PDGF- and TPA-Induced c-fosmRNA Expression and Increases the Formation of Phosphatidylethanolamine with a Shift from Less to More Polar Molecular Species in C3H/10T12 Cells

Cited by 4 publications

References 29 publications

Nuclear import of factors involved in signaling is inhibited in C3H/10T1/2 cells treated with tetradecylthioacetic acid

Nuclear import of factors involved in signaling is inhibited in C3H/10T1/2 cells treated with tetradecylthioacetic acid

RACK1 regulates Ki‐Ras‐mediated signaling and morphological transformation of NIH 3T3 cells

Chlorpromazine interaction with phosphatidylserines: A 13C and 31P solid-state NMR study

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