Novel Roles of Specific Isoforms of Protein Kinase C in Activation of the c-<i>fos</i> Serum Response Element

Soh, Jae-Won; Lee, Eun Hae; Prywes, Ron; Weinstein, I. Bernard

doi:10.1128/mcb.19.2.1313

Cited by 243 publications

(219 citation statements)

References 64 publications

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“…In the presence of actinomycin D, the effect of PMA on the overall and P3-dependent PTHrP expression was found to be reduced significantly ( Figure 1D), suggesting that PMA increased the transcriptional activity of the P3 promoter. In the presence of the MAPK/ERK kinase (MEK)-1 inhibitor PD98059, PMA failed to induce PTHrP expression ( Figure 1D), suggesting that, in MCF-7 cells, PMA mediates its effect on PTHrP, at least partially, by activating the Raf/MEK-1/ERK1/2 pathway [41]. We were able to demonstrate that PMA increased ERK1/2 phosphorylation and that this effect was inhibited by PD98059 (results not shown).…”

Section: Mcf-7 Cells Regulate Pthrp Expression Primarily Through the mentioning

confidence: 91%

“…To analyse the effect of these particular PKCs on P3 promoter activity, we used constitutively active forms of these kinases (PKCα-CAT and PKCε-CAT). PKCα-CAT and PKCε-CAT are truncated versions of PKCα and PKCε respectively [41]. They contain the C-terminal catalytic domain, but are lacking the N-terminal regulatory domain.…”

Section: A Constitutively Active Form Of Pkcε Mimics Pma In Its Abilimentioning

confidence: 99%

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Ets2 and protein kinase Cepsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells

Lindemann

Braig

Hauser

et al. 2003

Biochemical Journal

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Parathyroid hormone-related protein (PTHrP) promotes the metastatic potential and proliferation of breast cancer cells, and acts anti-apoptotically. In invasive MDA-MB-231 breast cancer cells, transforming growth factor β-regulated PTHrP synthesis is mediated by an Ets1/Smad3-dependent activation of the PTHrP P3 promoter. In the present study, we studied the regulation of PTHrP expression in non-invasive, Ets1-deficient and transforming growth factor β-resistant MCF-7 cells. We found PMA to be a strong stimulator of P3-dependent PTHrP expression in MCF-7 cells. Mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase 1 (MEK-1)/ERK1/2 inhibitor PD98059 interfered with this activity. Promoter studies revealed that the PMA effect depended on the Ets and stimulating protein-1 (Sp1)-binding sites. Of several Ets factors tested, Ets2, but not Ese-1, Elf-1 or Ets1, supported the PMA-dependent increase in promoter activity. PD98059 and a threonine to alanine mutation of the ERK1/2-responsive Ets2 phosphorylation site at position 72 inhibited the Ets2/PMA effect. Activated protein kinase C (PKC)ε could mimic PMA by stimulating the P3 promoter alone or in co-operation with Ets2 in an MEK-1/ERK1/2-dependent manner. Activated PKCα, although capable of co-operating with Ets2, failed to induce transcription from the P3 promoter on its own. The Ets2/PKCα synergistic effect was neither sensitive to PD98059 nor to Thr 72 /Ala 72 mutation. PMA neither increased the expression of Sp1 nor modulated the transcriptional activity of Sp1. However, it induced the displacement of a yet unknown factor from the Sp1-binding site, which may result in Sp1 recruitment to the promoter. Our results suggest an ERK1/2-dependent Ets2/PKCε synergism to be involved in PTHrP expression in MCF-7 breast cancer cells.

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Section: Mcf-7 Cells Regulate Pthrp Expression Primarily Through the mentioning

confidence: 91%

Section: A Constitutively Active Form Of Pkcε Mimics Pma In Its Abilimentioning

confidence: 99%

Ets2 and protein kinase Cepsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells

Lindemann

Braig

Hauser

et al. 2003

Biochemical Journal

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“…Wild-type mouse HSF1 or HSF2 were cloned into pHACE containing a C-terminal HA tag and pFLAGN1 containing an N-terminal FLAG tag (Soh et al, 1999). Internal deletion mutants were constructed in HSF1-containing pHACE vector by introducing two EcoRI sites into the HSF1 coding sequence using deletion primers.…”

Section: Plasmid and Constructsmentioning

confidence: 99%

A novel function for HSF1-induced mitotic exit failure and genomic instability through direct interaction between HSF1 and Cdc20

Lee

et al. 2007

Oncogene

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Although heat-shock factor (HSF) 1 is a known transcriptional factor of heat-shock proteins, other pathways like production of aneuploidy and increased protein stability of cyclin B1 have been proposed. In the present study, the regulatory domain of HSF1 (amino-acid sequence 212-380) was found to interact directly with the amino-acid sequence 106-171 of Cdc20. The association between HSF1 and Cdc20 inhibited the interaction between Cdc27 and Cdc20, the phosphorylation of Cdc27 and the ubiquitination activity of anaphase-promoting complex (APC). The overexpression of HSF1 inhibited mitotic exit and the degradations of cyclin B1 and securin, which resulted in production of aneuploidy and multinucleated cells, but regulatory domain-deficient HSF1 did not. Moreover, HSF1-overexpressing cells showed elevated levels of micronuclei and genomic alteration. The depletion of HSF1 from cells highly expressing HSF1 reduced nocodazole-mediated aneuploidy in cells. These findings suggest a novel function of HSF1 frequently overexpressed in cancer cells, to inhibit APC/C activity by interacting with Cdc20, and to result in aneuploidy development and genomic instability.

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“…The PLC␤2 expression vector was a gift from Dr. D. Wu (University of Connecticut Health Center, Farmington, CT). Preparation and characterization of the HA-tagged PKC␣, PKC␦, and PKC expression constructs were described in a previous publication (19 …”

Section: Expression Vectorsmentioning

confidence: 99%

Reconstitution of Chemotactic Peptide-Induced Nicotinamide Adenine Dinucleotide Phosphate (Reduced) Oxidase Activation in Transgenic COS-phox Cells

Nanamori

Sang

et al. 2004

The Journal of Immunology

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A whole-cell-based reconstitution system was developed to study the signaling mechanisms underlying chemoattractant-induced activation of NADPH oxidase. This system takes advantage of the lack of formyl peptide receptor-mediated response in COS-phox cells expressing gp91phox, p22phox, p67phox, and p47phox, which respond to phorbol ester and arachidonic acid with O⨪2 production. By exogenous expression of signaling molecules enriched in neutrophils, we have identified several critical components for fMLP-induced NADPH oxidase activation. Expression of PKCδ, but not PKCα, -βII, and -ζ, is necessary for the COS-phox cells to respond to fMLP. A role of PKCδ in neutrophil NADPH oxidase was confirmed based on the ability of fMLP to induce PKCδ translocation and the sensitivity of fMLP-induced O⨪2 production to rottlerin, a PKCδ-selective inhibitor. Optimal reconstitution also requires phospholipase C-β2 and PI3K-γ. We found that formyl peptide receptor could use the endogenous Rac1 as well as exogenous Rac1 and Rac2 for NADPH oxidase activation. Exogenous expression of p40phox potentiated fMLP-induced O⨪2 production and raised the level of O⨪2 in unstimulated cells. Collectively, these results provide first direct evidence for reconstituting fMLP-induced O⨪2 production in a nonhemopoietic cell line, and demonstrate the requirement of multiple signaling components for optimal activation of NADPH oxidase by a chemoattractant.

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Novel Roles of Specific Isoforms of Protein Kinase C in Activation of the c-fos Serum Response Element

Cited by 243 publications

References 64 publications

Ets2 and protein kinase Cepsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells

Ets2 and protein kinase Cepsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells

A novel function for HSF1-induced mitotic exit failure and genomic instability through direct interaction between HSF1 and Cdc20

Reconstitution of Chemotactic Peptide-Induced Nicotinamide Adenine Dinucleotide Phosphate (Reduced) Oxidase Activation in Transgenic COS-phox Cells

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