Protein Kinase C Is Required for Long-Lasting Synaptic Enhancement by the Neuropeptide DRNFLRFamide in Crayfish

1998 ◽  
Vol 79 (2) ◽  
pp. 1127-1131 ◽  
Author(s):  
Rainer W. Friedrich ◽  
G. F. Molnar ◽  
Michael Schiebe ◽  
A. Joffre Mercier
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Neuromuscular Junctions ◽  
Initial Increase ◽  
Excitatory Postsynaptic Potential ◽  
Signaling Systems ◽  
Synaptic Modulation ◽  
Kinase C ◽  
Extensor Muscles

Friedrich, Rainer W., G. F. Molnar, Michael Schiebe, and A. Joffre Mercier. Protein kinase C is required for long-lasting synaptic enhancement by the neuropeptide DRNFLRFamide in crayfish. J. Neurophysiol. 79: 1127–1131, 1998. The FMRFamide-related neuropeptide AspArgAsnPheLeuArgPhe-NH2 (DRNFLRFamide, DF2) induces a long-lasting enhancement of synaptic transmission at neuromuscular junctions on the crayfish deep abdominal extensor muscles. Here we investigated the function of protein kinase C (PKC) in this effect because PKC has been implied in the control of long-term synaptic modulation in other systems. The general kinase antagonist staurosporine reduced both the initial increase in excitatory postsynaptic potential (EPSP) amplitude and the duration of synaptic enhancement. Unlike staurosporine, the selective PKC inhibitors, chelerythrine and bisindolylmaleimide, augmented the initial EPSP increase. However, like staurosporine, they also reduced the duration of synaptic enhancement. The PKC activator, phorbol-12-myristate 13-acetate, induced a long-lasting synaptic enhancement that was blocked by chelerythrine. These results show that synaptic enhancement by DF2 is mediated by different intracellular signaling systems that act in temporal sequence. The initial increase in EPSP amplitudes is negatively regulated by PKC and involves another, staurosporine-sensitive, kinase; whereas, the maintenance of synaptic enhancement requires PKC.

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.

Endothelin activation of phospholipase D: dual modulation by protein kinase C and Ca2+

1993 ◽  
Vol 264 (5) ◽  
pp. F845-F853
Author(s):  
M. M. Friedlaender ◽  
D. Jain ◽  
Z. Ahmed ◽  
D. Hart ◽  
R. L. Barnett ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase D ◽  
Intracellular Signaling ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Kinase C ◽  
Eta Receptor ◽  
Ca2 Channels ◽  
Stimulation Of

Previous work from this laboratory has identified an endothelin (ET) type A (ETA) receptor on cultured rat renal medullary interstitial cells (RMIC), coupled to phosphatidylinositol-specific phospholipase C (PI-PLC), dihydropyridine-insensitive receptor-operated Ca2+ channels, and phospholipase A2. The current studies explored a role for ET stimulation of phosphatidylcholine-specific phospholipase D (PC-PLD) in intracellular signaling of this cell type. ET stimulated PLD activation, as measured by phosphatidic acid (PA) or phosphatidylethanol (PEt) accumulation, in a time- and concentration-dependent manner. Inhibition of diacylglycerol (DAG) kinase by ethylene glycol dioctanoate or 6-(2)4-[(4-fluorophenyl)-phenylmethylene]-1-piperadinyl]ethy l-7-methyl-5H - thiaxolo-[3,2-alpyrimidin]-5-one (R 59022) failed to blunt PA accumulation, indicating that PLD, and not DAG, was the source of PA. Inhibition of PA phosphohydrolase (PAP) by propranolol increased late accumulation of PA, suggesting that the prevailing metabolic flow was in the direction of PA to DAG. Phorbol 12-myristate 13-acetate (PMA) augmented ET-evoked PEt accumulation, whereas downregulation of protein kinase C (PKC) obviated agonist-induced PEt production. PMA augmentation of PLD activity proceeded independent of cytosolic free Ca2+ concentration. Ca2+ derived from either intracellular or extracellular sources enhanced ET-related PEt accumulation but was without effect in PKC-downregulated cells. Collectively, these observations indicate that ET stimulates PLD production in RMIC. PKC is the major regulator of this process, with Ca2+ playing a secondary, modulatory role. In addition, these data suggest that PC-PLD is coupled to the ETA receptor.

scholarly journals Aldosterone stimulates vacuolar H+-ATPase activity in renal acid-secretory intercalated cells mainly via a protein kinase C-dependent pathway

2011 ◽  
Vol 301 (5) ◽  
pp. C1251-C1261 ◽  
Author(s):  
Christian Winter ◽  
Nicole B. Kampik ◽  
Luca Vedovelli ◽  
Florina Rothenberger ◽  
Teodor G. Păunescu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Intracellular Signaling ◽  
Collecting Duct ◽  
Intercalated Cells ◽  
Nongenomic Action ◽  
Kinase C ◽  
Urinary Acidification ◽  
Stimulation Of

Urinary acidification in the collecting duct is mediated by the activity of H+-ATPases and is stimulated by various factors including angiotensin II and aldosterone. Classically, aldosterone effects are mediated via the mineralocorticoid receptor. Recently, we demonstrated a nongenomic stimulatory effect of aldosterone on H+-ATPase activity in acid-secretory intercalated cells of isolated mouse outer medullary collecting ducts (OMCD). Here we investigated the intracellular signaling cascade mediating this stimulatory effect. Aldosterone stimulated H+-ATPase activity in isolated mouse and human OMCDs. This effect was blocked by suramin, a general G protein inhibitor, and GP-2A, a specific Gαq inhibitor, whereas pertussis toxin was without effect. Inhibition of phospholipase C with U-73122, chelation of intracellular Ca2+ with BAPTA, and blockade of protein kinase C prevented the stimulation of H+-ATPases. Stimulation of PKC by DOG mimicked the effect of aldosterone on H+-ATPase activity. Similarly, aldosterone and DOG induced a rapid translocation of H+-ATPases to the luminal side of OMCD cells in vivo. In addition, PD098059, an inhibitor of ERK1/2 activation, blocked the aldosterone and DOG effects. Inhibition of PKA with H89 or KT2750 prevented and incubation with 8-bromoadenosine-cAMP mildly increased H+-ATPase activity. Thus, the nongenomic modulation of H+-ATPase activity in OMCD-intercalated cells by aldosterone involves several intracellular pathways and may be mediated by a Gαq protein-coupled receptor and PKC. PKA and cAMP appear to have a modulatory effect. The rapid nongenomic action of aldosterone may participate in the regulation of H+-ATPase activity and contribute to final urinary acidification.

scholarly journals Kisspeptin Activation of TRPC4 Channels in Female GnRH Neurons Requires PIP2 Depletion and cSrc Kinase Activation

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2772-2783 ◽  
Author(s):  
Chunguang Zhang ◽  
Martha A. Bosch ◽  
Oline K. Rønnekleiv ◽  
Martin J. Kelly
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trpc Channels ◽  
Kinase Activation ◽  
Trpc Channel ◽  
Kinase C ◽  
Gnrh Neurons

Abstract Kisspeptin signaling via its Gαq-coupled receptor GPR54 plays a crucial role in modulating GnRH neuronal excitability, which controls pituitary gonadotropins secretion and ultimately reproduction. Kisspeptin potently depolarizes GnRH neurons primarily through the activation of canonical transient receptor potential (TRPC) channels, but the intracellular signaling cascade has not been elucidated. Presently, we have established that kisspeptin activation of TRPC channels requires multiple membrane and intracellular signaling molecules. First, phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis by phospholipase Cβ is required because whole-cell dialysis of Dioctanoylglycerol-PIP2 (DiC8-PIP2) inhibited the kisspeptin activation of TRPC channels, and the phosphatidylinositol 4-kinase inhibitor wortmannin, which attenuates PIP2 synthesis, prolonged TRPC channel activation. Using single cell RT-PCR, we identified that the mRNA for the PIP2-interacting TRPC channel subunit, TRPC4α, is expressed in GnRH neurons. Depletion of intracellular Ca2+ stores by thapsigargin and inositol 1,4,5-trisphosphate had no effect, indicating that the TRPC channels are not store-operated. Neither removing extracellular Ca2+ nor buffering intracellular Ca2+ with EGTA or BAPTA had any effect on the kisspeptin activation of the TRPC channels. However, the Ca2+ channel blocker Ni2+ inhibited the kisspeptin-induced inward current. Moreover, inhibition of protein kinase C by bisindolylmaleimide-I or calphostin C had no effect, but activation of protein kinase C by phorbol 12,13-dibutyrate occluded the kisspeptin-activated current. Finally, inhibition of the cytoplasmic tyrosine kinase cSrc by genistein or the pyrazolo-pyrimidine PP2 blocked the activation of TRPC channels by kisspeptin. Therefore, TRPC channels in GnRH neurons are receptor-operated, and kisspeptin activates TRPC channels through PIP2 depletion and cSrc tyrosine kinase activation, which is a novel signaling pathway for peptidergic excitation of GnRH neurons.

scholarly journals Regulated expression of endothelin converting enzymes in glomerular endothelial cells.

1997 ◽  
Vol 8 (4) ◽  
pp. 580-585 ◽  
Author(s):  
K Uchida ◽  
S Uchida ◽  
K Nitta ◽  
W Yumura ◽  
H Nihei
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Mrna Stability ◽  
Ribonuclease Protection Assay ◽  
Signaling Systems ◽  
Control Value ◽  
Kinase C ◽  
Glomerular Endothelial Cells

Endothelin converting enzyme (ECE) constitutes a potential regulatory site for the production of active mature endothelins. Two cDNAs (ECE-1 and -2) encoding ECE have recently been cloned, but the regulation of the expression of these ECE has not been clarified. In the study presented here, an attempt was made to determine whether or not glomerular endothelial cells (GEN) express ECE-1 and -2, and to learn how the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems. Ribonuclease protection assay revealed the expression of ECE-1 and -2 in cultured GEN, and the expression was increased approximately 2.5- and approximately 1.8-fold, respectively, by treatment with 10(-7) M 12-O-tetradecanocyl-phorbol-13-acetate (TPA) for 4 hours. These increases in ECE-1 and -2 expression with TPA were inhibited by cotreatment with calphostin C (10(-7) M). In contrast, 24-h treatment with 10(-7) M TPA significantly decreased the expression of ECE-1 and -2, indicating that the expression was tightly regulated by protein kinase C (PKC)-dependent mechanism(s). Actinomycin D (1 microgram/mL) abolished the TPA-induced increase of ECE-1 and -2 mRNA, whereas TPA treatment did not affect the mRNA stability of ECE-1 and -2, thus suggesting that TPA-induced increases of ECE-1 and -2 mRNA resulted from the transcriptional activation of ECE-1 and -2, gene, rather than from the increase of mRNA stability. In addition to the regulation by PKC, the effects of protein kinase A and G on ECE-1 and -2 expression were also examined. Treatment with chlorophenyl-thio cyclic AMP (200 microM) for 24 h decreased ECE-1 and -2 expression to approximately 50% and approximately 40% of the control value, respectively. 8-bromo-3', 5'-cyclic GMP also decreased ECE-1 and -2 expression to approximately 80% and approximately 25% of the control value, respectively. These results demonstrate that the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems, with the most prominent regulatory effect shown by protein kinase C.

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 Intracellular signaling by protein kinase C.

1989 ◽  
Vol 33 (1) ◽  
pp. 33-37
Author(s):  
Hiroyoshi Hidaka ◽  
Takahisa Hachiya ◽  
Masatoshi Hagiwara ◽  
Masato Watanabe ◽  
Koji Onoda
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Kinase C

scholarly journals Role of Protein Kinase C in Diabetic Complications

2019 ◽  
Vol 7 (2) ◽  
pp. 87-95
Author(s):  
Simran ◽  
Amarjot Kaur Grewal ◽  
Sandeep Arora ◽  
Thakur Gurjeet Singh
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Diabetic Complications ◽  
Intracellular Signaling ◽  
Microvascular Complications ◽  
Polyol Pathway ◽  
Cellular Damage ◽  
Kinase C ◽  
Hexosamine Pathway ◽  
Systemic Disorder

Diabetes is the most common and systemic disorder associated with hyperglycemia which is the significant factor in the development of micro- and macrovascular changes. Many mechanistic approaches i.e. activation of Protein kinase C, glycation end products production, hexosamine pathway and polyol pathway induce cellular damage and lead to the development of diabetic complications like nephropathy, neuropathy, retinopathy, and myopathy. One of the adverse effects of long-lasting hyperglycemia is activation of PKC (intracellular signaling enzyme) and has become a field of great research interest. Hence, in this review special emphasis is placed on microvascular complications which are due to activation of PKC. Clinical trials have also been conducted using selective PKC inhibitors and have shown positive results against hyperglycemia.

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