Acceleration of trophoblast differentiation by heparin-binding EGF-like growth factor is dependent on the stage-specific activation of calcium influx by ErbB receptors in developing mouse blastocysts

Development ◽  
2000 ◽  
Vol 127 (1) ◽  
pp. 33-44 ◽  
Author(s):  
J. Wang ◽  
L. Mayernik ◽  
J.F. Schultz ◽  
D.R. Armant
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Erbb Receptors ◽  
Apical Surface ◽  
Heparin Binding ◽  
Trophoblast Cells ◽  
Trophoblast Differentiation ◽  
Kinase C

Heparin-binding EGF-like growth factor (HB-EGF) is expressed in the mouse endometrial epithelium during implantation exclusively at sites apposed to embryos and accelerates the development of cultured blastocysts, suggesting that it may regulate peri-implantation development in utero. We have examined the influence of HB-EGF on mouse trophoblast differentiation in vitro and the associated intracellular signaling pathways. HB-EGF both induced intracellular Ca2+ signaling and accelerated trophoblast development to an adhesion-competent stage, but only late on gestation day 4 after ErbB4, a receptor for HB-EGF, translocated from the cytoplasm to the apical surface of trophoblast cells. The acceleration of blastocyst differentiation by HB-EGF was attenuated after inhibition of protein tyrosine kinase activity or removal of surface heparan sulfate, as expected. Chelation of intracellular Ca2+ blocked the ability of HB-EGF to accelerate development, as did inhibitors of protein kinase C or calmodulin. The absence of any effect by a phospholipase C inhibitor and the requirement for extracellular Ca2+ suggested that the accrued free cytoplasmic Ca2+ did not originate from inositol phosphate-sensitive intracellular stores, but through Ca2+ influx. Indeed, N-type Ca2+ channel blockers specifically inhibited the ability of HB-EGF to both induce Ca2+ signaling and accelerate trophoblast development. We conclude that HB-EGF accelerates the differentiation of trophoblast cells to an adhesion-competent stage by inducing Ca2+ influx, which activates calmodulin and protein kinase C. An upstream role for ErbB4 in this pathway is implicated by the timing of its translocation to the trophoblast surface.

scholarly journals Induction of heparin-binding epidermal growth factor-like growth factor mRNA by protein kinase C activators

1994 ◽  
Vol 46 (3) ◽  
pp. 690-695 ◽  
Author(s):  
Mian-Shin Tan ◽  
Jer-Chia Tsai ◽  
Yau-Jiunn Lee ◽  
Hung-Chun Chen ◽  
Shyi-Jang Shin ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Heparin Binding ◽  
Kinase C ◽  
Protein Kinase C Activators ◽  
Epidermal Growth

scholarly journals Dissociation of nuclear events on p21 RAS transformation of FDC-P1 myeloid cells: c-jun/AP-1 expression versus c-myc transcription

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2404-2414
Author(s):  
S Litz-Jackson ◽  
AH Miller ◽  
GS Burgess ◽  
HS Boswell
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Myeloid Cells ◽  
Transcriptional Response ◽  
Ras Oncogene ◽  
Kinase C ◽  
P21 Ras ◽  
Protein Kinase C Activation

We have previously reported transformation to growth factor-independent proliferation in the interleukin-3 (IL-3)-dependent cell line FDC-P1 by high-level expression of the valine 12 Harvey RAS oncogene, following from a nonautocrine mechanism. The present study was undertaken to examine nuclear tertiary messenger, transcriptional response gene expression to deduce the intracellular signaling pathways responsible for this autonomous proliferation. We confirmed other reports that transformed p21RAS-expressing cells constitutively express the transcription factor complex jun/AP-1, in this case resulting from the ongoing expression of the c-jun and c-fos genes in the absence of IL-3. However, the ongoing growth factor independent expression of c-myc by a transcriptional mechanism in FDC-P1 cells expressing p21 RAS cannot be explained by intracellular signaling in the jun/AP-1 (protein kinase C) pathway. This conclusion derives from the observation that c-jun expression mediated via protein kinase C activation with phorbol ester (12–0-tetra decanoylphorbol-13-acetate, TPA) treatment does not lead to c-myc expression in parent FDC-P1 cells. On the contrary, FDC-P1 cells stably transfected with a c-myc gene controlled under the influence of a metallothionein IIA promoter (containing the TPA-responsive element [TRE]) express the transfected MTIIA-c-myc and downregulate the endogenous c-myc in response to protein kinase C activation with TPA. Further, nuclear proteins derived from cells expressing p21 RAS, which bind specifically to the purified c-myc P2 promoter, are not competed in their binding to the motif-rich P2 element by AP-1 oligonucleotide. Therefore, expression of the Harvey RAS oncogene in FDC-P1 myeloid cells leads to at least two pathways of cytoplasmic signaling. One pathway involves protein kinase C and c-jun/AP-1, but another pathway that is protein kinase C-independent appears to mediate c-myc transcription.

scholarly journals Convergence of Protein Kinase C and JAK-STAT Signaling on Transcription Factor GATA-4

2005 ◽  
Vol 25 (22) ◽  
pp. 9829-9844 ◽  
Author(s):  
Jun Wang ◽  
Pierre Paradis ◽  
Anne Aries ◽  
Hiba Komati ◽  
Chantal Lefebvre ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Binding Sites ◽  
Intracellular Signaling ◽  
Receptor Activation ◽  
Cardiomyocyte Hypertrophy ◽  
Transcriptional Responses ◽  
Stat Proteins ◽  
Kinase C

ABSTRACT Angiotensin II (AII), a potent vasoactive hormone, acts on numerous organs via G-protein-coupled receptors and elicits cell-specific responses. At the level of the heart, AII stimulation alters gene transcription and leads to cardiomyocyte hypertrophy. Numerous intracellular signaling pathways are activated in this process; however, which of these directly link receptor activation to transcriptional regulation remains undefined. We used the atrial natriuretic factor (ANF) gene (NPPA) as a marker to elucidate the signaling cascades involved in AII transcriptional responses. We show that ANF transcription is activated directly by the AII type 1 receptor and precedes the development of myocyte hypertrophy. This response maps to STAT and GATA binding sites, and the two elements transcriptionally cooperate to mediate signaling through the JAK-STAT and protein kinase C (PKC)-GATA-4 pathways. PKC phosphorylation enhances GATA-4 DNA binding activity, and STAT-1 functionally and physically interacts with GATA-4 to synergistically activate AII and other growth factor-inducible promoters. Moreover, GATA factors are able to recruit STAT proteins to target promoters via GATA binding sites, which are sufficient to support synergy. Thus, STAT proteins can act as growth factor-inducible coactivators of tissue-specific transcription factors. Interactions between STAT and GATA proteins may provide a general paradigm for understanding cell specificity of cytokine and growth factor signaling.

scholarly journals Dissociation of nuclear events on p21 RAS transformation of FDC-P1 myeloid cells: c-jun/AP-1 expression versus c-myc transcription

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2404-2414 ◽  
Author(s):  
S Litz-Jackson ◽  
AH Miller ◽  
GS Burgess ◽  
HS Boswell
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Myeloid Cells ◽  
Transcriptional Response ◽  
Ras Oncogene ◽  
Kinase C ◽  
P21 Ras ◽  
Protein Kinase C Activation

Abstract We have previously reported transformation to growth factor-independent proliferation in the interleukin-3 (IL-3)-dependent cell line FDC-P1 by high-level expression of the valine 12 Harvey RAS oncogene, following from a nonautocrine mechanism. The present study was undertaken to examine nuclear tertiary messenger, transcriptional response gene expression to deduce the intracellular signaling pathways responsible for this autonomous proliferation. We confirmed other reports that transformed p21RAS-expressing cells constitutively express the transcription factor complex jun/AP-1, in this case resulting from the ongoing expression of the c-jun and c-fos genes in the absence of IL-3. However, the ongoing growth factor independent expression of c-myc by a transcriptional mechanism in FDC-P1 cells expressing p21 RAS cannot be explained by intracellular signaling in the jun/AP-1 (protein kinase C) pathway. This conclusion derives from the observation that c-jun expression mediated via protein kinase C activation with phorbol ester (12–0-tetra decanoylphorbol-13-acetate, TPA) treatment does not lead to c-myc expression in parent FDC-P1 cells. On the contrary, FDC-P1 cells stably transfected with a c-myc gene controlled under the influence of a metallothionein IIA promoter (containing the TPA-responsive element [TRE]) express the transfected MTIIA-c-myc and downregulate the endogenous c-myc in response to protein kinase C activation with TPA. Further, nuclear proteins derived from cells expressing p21 RAS, which bind specifically to the purified c-myc P2 promoter, are not competed in their binding to the motif-rich P2 element by AP-1 oligonucleotide. Therefore, expression of the Harvey RAS oncogene in FDC-P1 myeloid cells leads to at least two pathways of cytoplasmic signaling. One pathway involves protein kinase C and c-jun/AP-1, but another pathway that is protein kinase C-independent appears to mediate c-myc transcription.

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