scholarly journals Protein Kinase C-Induced Early Growth Response Protein-1 Binding to SNAIL Promoter in Epithelial–Mesenchymal Transition of Human Embryonic Stem Cells

2014 ◽  
Vol 23 (18) ◽  
pp. 2180-2189 ◽  
Author(s):  
Masaki Kinehara ◽  
Suguru Kawamura ◽  
Sumiyo Mimura ◽  
Mika Suga ◽  
Akiko Hamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Early Growth ◽  
Mesenchymal Transition ◽  
Early Growth Response ◽  
Kinase C

scholarly journals Extracellular ATP stimulates the early growth response protein 1 (Egr-1) via a protein kinase C-dependent pathway in the human osteoblastic HOBIT cell line

2003 ◽  
Vol 373 (3) ◽  
pp. 815-824 ◽  
Author(s):  
Alex PINES ◽  
Milena ROMANELLO ◽  
Laura CESARATTO ◽  
Giuseppe DAMANTE ◽  
Luigi MORO ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Cytosolic Calcium ◽  
Early Growth ◽  
Extracellular Atp ◽  
Extracellular Nucleotides ◽  
Cell Physiology ◽  
Early Growth Response ◽  
Kinase C

Extracellular nucleotides exert an important role in controlling cell physiology by activating intracellular signalling cascades. Osteoblast HOBIT cells express P2Y1 and P2Y2 G-protein-coupled receptors, and respond to extracellular ATP by increasing cytosolic calcium concentrations. Early growth response protein 1 (Egr-1) is a C2H2-zinc-finger-containing transcriptional regulator responsible for the activation of several genes involved in the control of cell proliferation and apoptosis, and is thought to have a central role in osteoblast biology. We show that ATP treatment of HOBIT cells increases Egr-1 protein levels and binding activity via a mechanism involving a Ca2+-independent protein kinase C isoform. Moreover, hypotonic stress and increased medium turbulence, by inducing ATP release, result in a similar effect on Egr-1. Increased levels of Egr-1 protein expression and activity are achieved at very early times after stimulation (5 min), possibly accounting for a rapid way for changing the osteoblast gene-expression profile. A target gene for Egr-1 that is fundamental in osteoblast physiology, COL1A2, is up-regulated by ATP stimulation of HOBIT cells in a timescale that is compatible with that of Egr-1 activation.

scholarly journals Protein Kinase C β/Early Growth Response-1 Pathway

2006 ◽  
Vol 48 (9) ◽  
pp. A47-A55 ◽  
Author(s):  
Shi-Fang Yan ◽  
Evis Harja ◽  
Martin Andrassy ◽  
Tomoyuki Fujita ◽  
Ann Marie Schmidt
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response ◽  
Kinase C ◽  
Early Growth Response 1

scholarly journals The Protein Kinase C System Acts through the Early Growth Response Protein 1 to Increase LHβ Gene Expression in Synergy with Steroidogenic Factor-1

1999 ◽  
Vol 13 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Lisa M. Halvorson ◽  
Ursula B. Kaiser ◽  
William W. Chin
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Gene Promoter ◽  
Early Growth ◽  
Mrna Levels ◽  
Steroidogenic Factor 1 ◽  
Early Growth Response ◽  
Kinase C

Abstract Expression of the LHβ gene has been shown to be modulated by both the orphan nuclear receptor, steroidogenic factor-1 (SF-1), and the early growth response protein 1, Egr-1. It is also well known that LHβ mRNA levels are increased after hormonal activation of the protein kinase C (PKC) signaling system, for example by GnRH; however, the mechanisms by which the PKC system exerts this effect has not been fully characterized. By transient transfection of the GH3 cell line, we demonstrate that activation of the PKC system with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), increases activity of region −207/+5 of the rat LHβ gene promoter (∼2-fold) and markedly augments SF-1-induced stimulation (95-fold in the presence of both factors vs. 13-fold for SF-1 alone). Mutation of the two previously identified Egr-1 sites not only prevents Egr-1 effects on the LHβ gene promoter, but also eliminates the synergistic response to PMA and SF-1 together, findings that were confirmed in a longer construct spanning region −797/+5. In the gonadotrope-derived cell line,α T3–1, these mutations eliminate the GnRH responsiveness of the− 207/+5 LHβ promoter construct. We next show that PMA treatment (GH3 and αT3–1 cells) or GnRH treatment (αT3–1 cells) induces expression of Egr-1, as detected by Egr-1 interaction with Egr-1 DNA-binding sites in the rat LHβ gene promoter sequence. Furthermore, we demonstrate that PMA increases steady-state Egr-1 mRNA levels via increased Egr-1 transcription. We conclude that PMA-induced stimulation of LHβ gene expression is achieved, at least in part, by induction of Egr-1 expression.

scholarly journals Protein kinase C inhibitors override ZEB1-induced chemoresistance in HCC

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Rahul Sreekumar ◽  
Muhammad Emaduddin ◽  
Hajir Al-Saihati ◽  
Karwan Moutasim ◽  
James Chan ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapeutic Agents ◽  
Tumour Cells ◽  
Mesenchymal Transition ◽  
Kinase C ◽  
Pkc Inhibitors ◽  
Hcc Cells

Abstract Epithelial–mesenchymal transition (EMT) is a process by which tumour cells lose epithelial characteristics, become mesenchymal and highly motile. EMT pathways also induce stem cell features and resistance to apoptosis. Identifying and targeting this pool of tumour cells is a major challenge. Protein kinase C (PKC) inhibition has been shown to eliminate breast cancer stem cells but has never been assessed in hepatocellular cancer (HCC). We investigated ZEB family of EMT inducer expression as a biomarker for metastatic HCC and evaluated the efficacy of PKC inhibitors for HCC treatment. We showed that ZEB1 positivity predicted patient survival in multiple cohorts and also validated as an independent biomarker of HCC metastasis. ZEB1-expressing HCC cell lines became resistant to conventional chemotherapeutic agents and were enriched in CD44high/CD24low cell population. ZEB1- or TGFβ-induced EMT increased PKCα abundance. Probing public databases ascertained a positive association of ZEB1 and PKCα expression in human HCC tumours. Inhibition of PKCα activity by small molecule inhibitors or by PKCA knockdown reduced viability of mesenchymal HCC cells in vitro and in vivo. Our results suggest that ZEB1 expression predicts survival and metastatic potential of HCC. Chemoresistant/mesenchymal HCC cells become addicted to PKC pathway and display sensitivity to PKC inhibitors such as UCN-01. Stratifying patients according to ZEB1 and combining UCN-01 with conventional chemotherapy may be an advantageous chemotherapeutic strategy.

scholarly journals Self-Renewal Versus Lineage Commitment of Embryonic Stem Cells: Protein Kinase C Signaling Shifts the Balance

Stem Cells ◽  
2011 ◽  
Vol 29 (4) ◽  
pp. 618-628 ◽  
Author(s):  
Debasree Dutta ◽  
Soma Ray ◽  
Pratik Home ◽  
Melissa Larson ◽  
Michael W. Wolfe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Kinase C ◽  
Embryonic Stem Cells ◽  
Protein Kinase ◽  
Embryonic Stem ◽  
Lineage Commitment ◽  
Self Renewal ◽  
Kinase C

scholarly journals Protein Kinase C Signaling Transduces Endorphin-Primed Cardiogenesis in GTR1 Embryonic Stem Cells

2003 ◽  
Vol 92 (6) ◽  
pp. 617-622 ◽  
Author(s):  
Carlo Ventura ◽  
Elisabetta Zinellu ◽  
Emiliana Maninchedda ◽  
Marina Fadda ◽  
Margherita Maioli
Keyword(s):  
Stem Cells ◽  
Protein Kinase C ◽  
Embryonic Stem Cells ◽  
Protein Kinase ◽  
Embryonic Stem ◽  
Kinase C

scholarly journals Carbonic Anhydrase XII Expression Is Modulated during Epithelial Mesenchymal Transition and Regulated through Protein Kinase C Signaling

2020 ◽  
Vol 21 (3) ◽  
pp. 715 ◽  
Author(s):  
Daniele Vergara ◽  
Sara Ravaioli ◽  
Eugenio Fonzi ◽  
Loredaria Adamo ◽  
Marina Damato ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Carbonic Anhydrase ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Epithelial Mesenchymal Transition ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Kinase C ◽  
Pkc Activation

Members of the carbonic anhydrase family are functionally involved in the regulation of intracellular and extracellular pH in physiological and pathological conditions. Their expression is finely regulated to maintain a strict control on cellular homeostasis, and it is dependent on the activation of extracellular and intracellular signaling pathways. Combining RNA sequencing (RNA-seq), NanoString, and bioinformatics data, we demonstrated that the expression of carbonic anhydrase 12 (CAXII) is significantly different in luminal and triple negative breast cancer (BC) models and patients, and is associated with the activation of an epithelial mesenchymal transition (EMT) program. In BC models, the phorbol ester 12-myristate 13-acetate (PMA)-mediated activation of protein kinase C (PKC) induced a down-regulation of CAXII with a concomitant modulation of other members of the transport metabolon, including CAIX and the sodium bicarbonate cotransporter 3 (NBCn1). This is associated with a remodeling of tumor glycolytic metabolism induced after PKC activation. Overall, this analysis highlights the dynamic nature of transport metabolom and identifies signaling pathways finely regulating this plasticity.

Sign in / Sign up

Export Citation Format

Share Document